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Are E6 and E7 Oncoproteins the Key Modulators of Radiosensitivity in HPV 16 and 18 Carcinoma Cell Lines?
I. J. Radiation Oncology d Biology d Physics
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Volume 72, Number 1, Supplement, 2008
Aurora Kinases as Targets for Radiation Therapy in Prostate Cancer
M. Siedow, M. Zhang, G. Saia, K. Palanichamy, A. Chakravarti Massachusetts General Hospital, Boston, MA Purpose/Objective(s): The Aurora kinases represent a novel family of serine/threonine kinases critical for cell cycle control. As knowledge of the roles that the Aurora kinases play in mitotic events continues to grow, so too does the interest in targeting these kinases therapeutically. In this report, we explore the use of irradiation in combination with an Aurora kinase inhibitor in prostate cancer cell lines. Materials/Methods: We use a commercially available Aurora kinase inhibitor (EMD Biosciences) to inhibit the activity of both Aurora A and Aurora B in human DU-145 and PC-3 prostate cancer models. We also use siRNA to knock down Aurora A and/or Aurora B in prostate cancer cells. Radiosensitivities are compared in Aurora kinase-inhibited cells and in control cells. Results: We demonstrate that use of an inhibitor that targets the activity of both Aurora A and Aurora B can sensitize the prostate cancer cell lines DU-145 and PC-3 to irradiation, as indicated by a decreased cell viability and a reduced clonogenic survival in Aurora kinase inhibitor treated cells compared with control cells. This inhibitor induces cell death through polyploidy resulting in mitotic catastrophe. Using siRNA we also show that the inhibitor phenotype is not duplicated with Aurora A knockdown, but is readily visible in Aurora B knockdown and double knockdown cells. Individual knockdown of Aurora A or Aurora B was found to increase radiation sensitivity in prostate cancer cells. Furthermore, it is by two different mechanisms that cell death occurs, with Aurora A knockdown triggering caspase-mediated apoptosis while Aurora B knockdown inducing caspase-independent mitotic catastrophe. We have also shown that use of an Aurora kinase inhibitor with irradiation can significantly reduce tumor formation in athymic nu/nu mice. Conclusions: Our data suggests that the Aurora kinases are potential therapeutic targets for radiation sensitization in prostate cancer. Author Disclosure: M. Siedow, None; M. Zhang, None; G. Saia, None; K. Palanichamy, None; A. Chakravarti, None.
3201
The Efficacy of Low Dose Epigenetic Agents in Combination with Ionizing Radiation in a Neurosphere Tumor Model of Glioblastoma Multiforme
S. H. Lin1, H. Tsai1, A. Vescovi2, J. J. Laterra3, T. L. DeWeese1, S. B. Baylin1 1 The Johns Hopkins University School of Medicine, Baltimore, MD, 2University of Milan Bicocca, Milan, Italy, 3The Kennedy Krieger Institute, Baltimore, MD
Purpose/Objective(s): Promoter hypermethylation is a common mechanism that many cancers, including glioblastoma (GBM), use to silence critical genes that dictate growth and response to conventional therapies. Epigenetic drugs that target these processes are attractive candidates to use in combination with radiotherapy. We sought to determine the efficacy of low doses of the demethylating agent 5’-aza-2-deoxycytidine (DAC) and the nonselective histone deacetylase inhibitor Trichostatin (TSA), each tested alone, together, or in combination with radiation in a model of GBM. Materials/Methods: The GBM neurosphere line, 20913, grown under serum-free conditions was used. Neurospheres were treated for 96 hours. TSA is introduced sequentially in the last 18 hours of drug treatment. Clonogenic survival was assessed by neurosphere formation assay and apoptosis with annexin V staining. Tumor growth was initiated by stereotactic injection of treated cells into the striatum of SCID mice. Radiation sensitivity was tested with a single dose of 2 Gy. MGMT expression was determined by real time PCR. Statistics were performed using the student t test and Kaplan-Meier survival analysis and log-rank test. Results: DAC at 500 nM and 100 nM significantly inhibited clonogenicity (99 ± 2% and 66 ± 18%, respectively, p \ 0.0001 compared to mock), but was not seen at lower doses (10 and 1 nM). However MGMT re-expression was only induced with 500 nM DAC. TSA at 300 nM induces significant inhibition of clonogenicity (28% ± 24%, p = 0.03), which was not seen at lower doses ranging from 50 nM to 150 nM (0% to 11% ± 11%, p = 0.8). Combining 100 nM DAC and 150 nM TSA synergistically inhibited both neurosphere growth (84 ± 5%, p\0.0001) and enhanced apoptosis (59% ± 2%, p\0.0001 relative to mock). These effects were significantly better than treatment with either drug alone. Radiation induced apoptosis was also enhanced by this drug combination (66%) compared to radiation alone (11%) or either drugs alone (150 nM TSA = 50%; 100 nM DAC = 11%). We next tested whether this drug combination could inhibit tumor growth in vivo. The median survival of animals injected with mock treat cells is 81 days, which was significantly improved when cells were pretreated with 100 nM DAC or 150 nM TSA (95 vs. 94 days, respectively, p = 0.002). Interestingly, the median survival has not been reached for animals injected with cells pretreated with both agents together (4 of 5 animals alive at 106 days postinjection). Conclusions: Low dose epigenetic drugs are effective in inhibiting growth of GBM neurospheres, a combination that also enhances radiation-induced apoptosis. Epigenetic agents may provide a promising new avenue in the treatment of GBM, both in the concurrent setting with radiotherapy and in the adjuvant setting as well. Author Disclosure: S.H. Lin, None; H. Tsai, None; A. Vescovi, None; J.J. Laterra, None; T.L. DeWeese, None; S.B. Baylin, None.
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Are E6 and E7 Oncoproteins the Key Modulators of Radiosensitivity in HPV 16 and 18 Carcinoma Cell Lines?
H. K. Lord1, D. Violot1, D. Biard2, J. Bourhis1, M. Vozenin-Brotons1, E. Deutsch1 1 UPRES EA 27-10 Institute Gustave Roussy, Villejuif, France, 2Institut de Radiobiologie, Cellulaire et Mole´culaire, Fontenay aux Roses, France
Purpose/Objective(s): HPV-16 and 18 related malignancies lead to significant morbidity and mortality worldwide. Radiotherapy is the primary modality of treatment for these cancers, but outcomes remain suboptimal. Enhancing the therapeutic ratio of ionizing radiation is one potential way of improving results. Work by Abdulkarim et al., (1) has shown that an antiviral agent, cidofovir, has
Proceedings of the 50th Annual ASTRO Meeting the ability to down regulate E6 and E7 expression, to increase p53 and pRb levels, and to increase radiosensitivity in vitro and in vivo in HPV positive cells. We hypothesize that direct inactivation of E6 and E7 could trigger increased sensitivity to ionizing radiation and we aim to clarify this in our study. Materials/Methods: Human cervical carcinoma HPV-18 cells (HeLa) and murine lung carcinoma HPV-16 cells (TC -1) have been engineered with shRNA E6 and E7 EBV plasmid to selectively decrease oncoprotein expression, using the method developed by D Biard (2). Three different plasmids for E6 and E7 were used, and lines selected with Hygromycin B at a concentration of 125ml/ml. DMEM culture with 10% FBS, 1% Hepes Buffer and 1% penicillin and streptomycin was used. Two plasmid lines for E6 and E7 with adequate growth were then chosen. E6 and E7 expression was monitored using PCR and Western Blot techniques. Modulation of intrinsic radiosensitivity was assessed in vitro after exposure to 2 Gy, 4 Gy and 6 Gy of ionizing radiation. Results: We have confirmed successful knock down of E6 and E7 in Hela cells, with 80% reduction in levels on PCR and an absent band on Western Blot compared to control. Initial experiments with clonogenic survival assays have shown that for E6 and E7 knocked down HeLa cells, exposure to radiation produces significantly increased radiosensitivity. The survival fraction (SF2) for the control line was normalized to 100%, and for the two E6 lines there was 60% and 11%, and for the E7 lines 38% and 41% clonal survival. Conclusions: The functional impact of E6 and E7 knock down will be assessed by measuring p53, p21 and pRb levels with Western Blot. The alteration of DNA repair process and cell cycle distribution in the knocked down cells will also be measured using standard techniques. In vivo studies will be performed to assess tumor growth delay after exposure to ionizing radiation alone, cidofovir alone and the two treatments combined. These early data have identified E6 and E7 as primary modulators of radiosensitivity in HPV 18 carcinoma cell lines, but further results are due. Reference: 1. Abdulkarim B, et al., ‘‘Antiviral agent Cidofovir restores p53 function and enhances the radiosensitivity in HPV-associated cancers’’ Oncogene Vol 21 No 15, pp2334-2346. 2. Biard DSF ‘‘Untangling the relationships between DNA repair pathways by silencing more than 20 DNA repair genes in human stable clones’’ Nucleic Acids Research 2007 Vol 35 3535-3550. Author Disclosure: H.K. Lord, None; D. Violot, None; D. Biard, None; J. Bourhis, None; M. Vozenin-Brotons, None; E. Deutsch, None.
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Modulation of Radiation Response of Non-small Cell Lung Cancer Cells with Poly (ADP-Ribose) Polymerase Inhibitor: ABT-888
W. A. Hall1, L. Wang1, J. Clarke1, G. Otterson1, J. Z. Wang1, M. Villalona1, T. Hoang2, N. Mayr1, P. Ross1, J. C. Grecula1 1
Ohio State University, Columbus, OH, 2University of Wisconsin, Madison, WI
Purpose/Objective(s): The family of poly (ADP-ribose) polymerase (PARP) enzymes have been implicated in many important cellular processes including repairing DNA damage caused by various injury factors such as chemotherapy or radiation. The DNA repair process involves a rapid activation of PARPs by DNA strand breaks, poly (ADP-ribose) lation of PARPs as well as histone and other nuclear kinases, and recruitment of repair enzymes. ABT-888 is a potent inhibitor of PARP-1 and 2 enzymes. Although as single agent, it has no anti-proliferative effect, it has been shown that ABT-888 augmented the antitumor activity of DNA-damage drugs in various human tumors in preclinical studies. Primary objective of this research was to determine if the PARP inhibitor ABT-888 through its anti-DNA repair mechanism would enhance the killing effect of ionizing radiation in 3 non-small-cell cancer cell lines. Secondary objectives were to study cell-cycle progression and apoptosis as contributing factors. Materials/Methods: Three cell lines of non-small-cell lung cancer (NSCLC), A549, H460, and A549+E6W, were treated with ABT-888 (5 mmol/L) just before irradiation. Cells were irradiated with 0, 2, 4, or 6 Gy utilizing a Cs-137 cell irradiator. Clonogenic survival assays were used to evaluate the radiosensitizing effect of ABT-888 on NSCLC. Two tailed t test was utilized for statistical analysis. Flow cytometry for cell-cycle progression, and Western blotting of caspase 3 (key mediator of apoptosis) and PARP were performed to identify the mechanisms underlying the enhancing effects. Results: The combination of ABT-888 and radiation, compared with radiation alone, showed significant enhancement on radiation-induced clonogenic inhibition of H460, A549, and A549+E6W cells. Clonogenic survival was dose dependent. Surviving Fraction at 4 Gy for ABT-888 + radiation vs. radiation alone was 9.0% vs. 29.5% (p \ 0.001), 11.6% vs. 33.4% (p = 0.001), and 16.6% vs. 37.5% (p = 0.075), for the three cell lines, respectively. Surviving Fraction at 6 Gy for ABT-888 + radiation vs. radiation alone was 0.45% vs. 3.9% (p \ 0.001), 1.5% vs. 5.8% (p = 0.003) and 4.5% vs. 13.2% (p = 0.017) for the three cell lines, respectively. Results from flow cytometry indicated that ABT-888 induced cell cycle G2/M arrest at 24 hrs. Immunoblot analysis of caspase-3 and PARP revealed apoptosis and inhibition of PAR also contributed to increased cell death. Conclusions: These in vitro results indicate that ABT-888 sensitizes non-small-cell lung cancer cell lines to radiation, and the mechanisms include cell-cycle G2/M arrest, apoptosis, and inhibition of poly(ADP-ribose) polymerase. *Supported in part by NCI N01-CM-62207, NCI 5 P30 CA016058, and the George Condos Memorial Fund. Author Disclosure: W.A. Hall, None; L. Wang, None; J. Clarke, None; G. Otterson, None; J.Z. Wang, None; M. Villalona, None; T. Hoang, None; N. Mayr, None; P. Ross, None; J.C. Grecula, None.
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Higher Efficacy of ON01910.Na as a Potent Radiosensitizer than Cisplatin on Human Cervical Carcinoma Cells
L. Agoni1, I. Basu1, E. P. Reddy2, A. Alfieri3, C. Guha3 1 Albert Einstein College of Medicine, Bronx, NY, 2Fels Institute for Cancer Research & Molecular Biology, Temple University School of Medicine, Philadelphia, PA, 3Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY
Purpose/Objective(s): Cervical cancer is a major worldwide issue in woman’s health care with 5-year overall survival rate as low as 50% in many countries. Although, Cisplatin is the preferred chemotherapeutic agent for cervical malignancies, additional drugs with
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Volume 72, Number 1, Supplement, 2008
Aurora Kinases as Targets for Radiation Therapy in Prostate Cancer
M. Siedow, M. Zhang, G. Saia, K. Palanichamy, A. Chakravarti Massachusetts General Hospital, Boston, MA Purpose/Objective(s): The Aurora kinases represent a novel family of serine/threonine kinases critical for cell cycle control. As knowledge of the roles that the Aurora kinases play in mitotic events continues to grow, so too does the interest in targeting these kinases therapeutically. In this report, we explore the use of irradiation in combination with an Aurora kinase inhibitor in prostate cancer cell lines. Materials/Methods: We use a commercially available Aurora kinase inhibitor (EMD Biosciences) to inhibit the activity of both Aurora A and Aurora B in human DU-145 and PC-3 prostate cancer models. We also use siRNA to knock down Aurora A and/or Aurora B in prostate cancer cells. Radiosensitivities are compared in Aurora kinase-inhibited cells and in control cells. Results: We demonstrate that use of an inhibitor that targets the activity of both Aurora A and Aurora B can sensitize the prostate cancer cell lines DU-145 and PC-3 to irradiation, as indicated by a decreased cell viability and a reduced clonogenic survival in Aurora kinase inhibitor treated cells compared with control cells. This inhibitor induces cell death through polyploidy resulting in mitotic catastrophe. Using siRNA we also show that the inhibitor phenotype is not duplicated with Aurora A knockdown, but is readily visible in Aurora B knockdown and double knockdown cells. Individual knockdown of Aurora A or Aurora B was found to increase radiation sensitivity in prostate cancer cells. Furthermore, it is by two different mechanisms that cell death occurs, with Aurora A knockdown triggering caspase-mediated apoptosis while Aurora B knockdown inducing caspase-independent mitotic catastrophe. We have also shown that use of an Aurora kinase inhibitor with irradiation can significantly reduce tumor formation in athymic nu/nu mice. Conclusions: Our data suggests that the Aurora kinases are potential therapeutic targets for radiation sensitization in prostate cancer. Author Disclosure: M. Siedow, None; M. Zhang, None; G. Saia, None; K. Palanichamy, None; A. Chakravarti, None.
3201
The Efficacy of Low Dose Epigenetic Agents in Combination with Ionizing Radiation in a Neurosphere Tumor Model of Glioblastoma Multiforme
S. H. Lin1, H. Tsai1, A. Vescovi2, J. J. Laterra3, T. L. DeWeese1, S. B. Baylin1 1 The Johns Hopkins University School of Medicine, Baltimore, MD, 2University of Milan Bicocca, Milan, Italy, 3The Kennedy Krieger Institute, Baltimore, MD
Purpose/Objective(s): Promoter hypermethylation is a common mechanism that many cancers, including glioblastoma (GBM), use to silence critical genes that dictate growth and response to conventional therapies. Epigenetic drugs that target these processes are attractive candidates to use in combination with radiotherapy. We sought to determine the efficacy of low doses of the demethylating agent 5’-aza-2-deoxycytidine (DAC) and the nonselective histone deacetylase inhibitor Trichostatin (TSA), each tested alone, together, or in combination with radiation in a model of GBM. Materials/Methods: The GBM neurosphere line, 20913, grown under serum-free conditions was used. Neurospheres were treated for 96 hours. TSA is introduced sequentially in the last 18 hours of drug treatment. Clonogenic survival was assessed by neurosphere formation assay and apoptosis with annexin V staining. Tumor growth was initiated by stereotactic injection of treated cells into the striatum of SCID mice. Radiation sensitivity was tested with a single dose of 2 Gy. MGMT expression was determined by real time PCR. Statistics were performed using the student t test and Kaplan-Meier survival analysis and log-rank test. Results: DAC at 500 nM and 100 nM significantly inhibited clonogenicity (99 ± 2% and 66 ± 18%, respectively, p \ 0.0001 compared to mock), but was not seen at lower doses (10 and 1 nM). However MGMT re-expression was only induced with 500 nM DAC. TSA at 300 nM induces significant inhibition of clonogenicity (28% ± 24%, p = 0.03), which was not seen at lower doses ranging from 50 nM to 150 nM (0% to 11% ± 11%, p = 0.8). Combining 100 nM DAC and 150 nM TSA synergistically inhibited both neurosphere growth (84 ± 5%, p\0.0001) and enhanced apoptosis (59% ± 2%, p\0.0001 relative to mock). These effects were significantly better than treatment with either drug alone. Radiation induced apoptosis was also enhanced by this drug combination (66%) compared to radiation alone (11%) or either drugs alone (150 nM TSA = 50%; 100 nM DAC = 11%). We next tested whether this drug combination could inhibit tumor growth in vivo. The median survival of animals injected with mock treat cells is 81 days, which was significantly improved when cells were pretreated with 100 nM DAC or 150 nM TSA (95 vs. 94 days, respectively, p = 0.002). Interestingly, the median survival has not been reached for animals injected with cells pretreated with both agents together (4 of 5 animals alive at 106 days postinjection). Conclusions: Low dose epigenetic drugs are effective in inhibiting growth of GBM neurospheres, a combination that also enhances radiation-induced apoptosis. Epigenetic agents may provide a promising new avenue in the treatment of GBM, both in the concurrent setting with radiotherapy and in the adjuvant setting as well. Author Disclosure: S.H. Lin, None; H. Tsai, None; A. Vescovi, None; J.J. Laterra, None; T.L. DeWeese, None; S.B. Baylin, None.
3202
Are E6 and E7 Oncoproteins the Key Modulators of Radiosensitivity in HPV 16 and 18 Carcinoma Cell Lines?
H. K. Lord1, D. Violot1, D. Biard2, J. Bourhis1, M. Vozenin-Brotons1, E. Deutsch1 1 UPRES EA 27-10 Institute Gustave Roussy, Villejuif, France, 2Institut de Radiobiologie, Cellulaire et Mole´culaire, Fontenay aux Roses, France
Purpose/Objective(s): HPV-16 and 18 related malignancies lead to significant morbidity and mortality worldwide. Radiotherapy is the primary modality of treatment for these cancers, but outcomes remain suboptimal. Enhancing the therapeutic ratio of ionizing radiation is one potential way of improving results. Work by Abdulkarim et al., (1) has shown that an antiviral agent, cidofovir, has
Proceedings of the 50th Annual ASTRO Meeting the ability to down regulate E6 and E7 expression, to increase p53 and pRb levels, and to increase radiosensitivity in vitro and in vivo in HPV positive cells. We hypothesize that direct inactivation of E6 and E7 could trigger increased sensitivity to ionizing radiation and we aim to clarify this in our study. Materials/Methods: Human cervical carcinoma HPV-18 cells (HeLa) and murine lung carcinoma HPV-16 cells (TC -1) have been engineered with shRNA E6 and E7 EBV plasmid to selectively decrease oncoprotein expression, using the method developed by D Biard (2). Three different plasmids for E6 and E7 were used, and lines selected with Hygromycin B at a concentration of 125ml/ml. DMEM culture with 10% FBS, 1% Hepes Buffer and 1% penicillin and streptomycin was used. Two plasmid lines for E6 and E7 with adequate growth were then chosen. E6 and E7 expression was monitored using PCR and Western Blot techniques. Modulation of intrinsic radiosensitivity was assessed in vitro after exposure to 2 Gy, 4 Gy and 6 Gy of ionizing radiation. Results: We have confirmed successful knock down of E6 and E7 in Hela cells, with 80% reduction in levels on PCR and an absent band on Western Blot compared to control. Initial experiments with clonogenic survival assays have shown that for E6 and E7 knocked down HeLa cells, exposure to radiation produces significantly increased radiosensitivity. The survival fraction (SF2) for the control line was normalized to 100%, and for the two E6 lines there was 60% and 11%, and for the E7 lines 38% and 41% clonal survival. Conclusions: The functional impact of E6 and E7 knock down will be assessed by measuring p53, p21 and pRb levels with Western Blot. The alteration of DNA repair process and cell cycle distribution in the knocked down cells will also be measured using standard techniques. In vivo studies will be performed to assess tumor growth delay after exposure to ionizing radiation alone, cidofovir alone and the two treatments combined. These early data have identified E6 and E7 as primary modulators of radiosensitivity in HPV 18 carcinoma cell lines, but further results are due. Reference: 1. Abdulkarim B, et al., ‘‘Antiviral agent Cidofovir restores p53 function and enhances the radiosensitivity in HPV-associated cancers’’ Oncogene Vol 21 No 15, pp2334-2346. 2. Biard DSF ‘‘Untangling the relationships between DNA repair pathways by silencing more than 20 DNA repair genes in human stable clones’’ Nucleic Acids Research 2007 Vol 35 3535-3550. Author Disclosure: H.K. Lord, None; D. Violot, None; D. Biard, None; J. Bourhis, None; M. Vozenin-Brotons, None; E. Deutsch, None.
3203
Modulation of Radiation Response of Non-small Cell Lung Cancer Cells with Poly (ADP-Ribose) Polymerase Inhibitor: ABT-888
W. A. Hall1, L. Wang1, J. Clarke1, G. Otterson1, J. Z. Wang1, M. Villalona1, T. Hoang2, N. Mayr1, P. Ross1, J. C. Grecula1 1
Ohio State University, Columbus, OH, 2University of Wisconsin, Madison, WI
Purpose/Objective(s): The family of poly (ADP-ribose) polymerase (PARP) enzymes have been implicated in many important cellular processes including repairing DNA damage caused by various injury factors such as chemotherapy or radiation. The DNA repair process involves a rapid activation of PARPs by DNA strand breaks, poly (ADP-ribose) lation of PARPs as well as histone and other nuclear kinases, and recruitment of repair enzymes. ABT-888 is a potent inhibitor of PARP-1 and 2 enzymes. Although as single agent, it has no anti-proliferative effect, it has been shown that ABT-888 augmented the antitumor activity of DNA-damage drugs in various human tumors in preclinical studies. Primary objective of this research was to determine if the PARP inhibitor ABT-888 through its anti-DNA repair mechanism would enhance the killing effect of ionizing radiation in 3 non-small-cell cancer cell lines. Secondary objectives were to study cell-cycle progression and apoptosis as contributing factors. Materials/Methods: Three cell lines of non-small-cell lung cancer (NSCLC), A549, H460, and A549+E6W, were treated with ABT-888 (5 mmol/L) just before irradiation. Cells were irradiated with 0, 2, 4, or 6 Gy utilizing a Cs-137 cell irradiator. Clonogenic survival assays were used to evaluate the radiosensitizing effect of ABT-888 on NSCLC. Two tailed t test was utilized for statistical analysis. Flow cytometry for cell-cycle progression, and Western blotting of caspase 3 (key mediator of apoptosis) and PARP were performed to identify the mechanisms underlying the enhancing effects. Results: The combination of ABT-888 and radiation, compared with radiation alone, showed significant enhancement on radiation-induced clonogenic inhibition of H460, A549, and A549+E6W cells. Clonogenic survival was dose dependent. Surviving Fraction at 4 Gy for ABT-888 + radiation vs. radiation alone was 9.0% vs. 29.5% (p \ 0.001), 11.6% vs. 33.4% (p = 0.001), and 16.6% vs. 37.5% (p = 0.075), for the three cell lines, respectively. Surviving Fraction at 6 Gy for ABT-888 + radiation vs. radiation alone was 0.45% vs. 3.9% (p \ 0.001), 1.5% vs. 5.8% (p = 0.003) and 4.5% vs. 13.2% (p = 0.017) for the three cell lines, respectively. Results from flow cytometry indicated that ABT-888 induced cell cycle G2/M arrest at 24 hrs. Immunoblot analysis of caspase-3 and PARP revealed apoptosis and inhibition of PAR also contributed to increased cell death. Conclusions: These in vitro results indicate that ABT-888 sensitizes non-small-cell lung cancer cell lines to radiation, and the mechanisms include cell-cycle G2/M arrest, apoptosis, and inhibition of poly(ADP-ribose) polymerase. *Supported in part by NCI N01-CM-62207, NCI 5 P30 CA016058, and the George Condos Memorial Fund. Author Disclosure: W.A. Hall, None; L. Wang, None; J. Clarke, None; G. Otterson, None; J.Z. Wang, None; M. Villalona, None; T. Hoang, None; N. Mayr, None; P. Ross, None; J.C. Grecula, None.
3204
Higher Efficacy of ON01910.Na as a Potent Radiosensitizer than Cisplatin on Human Cervical Carcinoma Cells
L. Agoni1, I. Basu1, E. P. Reddy2, A. Alfieri3, C. Guha3 1 Albert Einstein College of Medicine, Bronx, NY, 2Fels Institute for Cancer Research & Molecular Biology, Temple University School of Medicine, Philadelphia, PA, 3Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY
Purpose/Objective(s): Cervical cancer is a major worldwide issue in woman’s health care with 5-year overall survival rate as low as 50% in many countries. Although, Cisplatin is the preferred chemotherapeutic agent for cervical malignancies, additional drugs with
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