The Combination of Olaparib and Camptothecin Effectively Sensitize Radiation

Abstract

anticancer therapy, and radiation-induced autophagy contributes to resistance of cancer cells to ionizing radiation (IR). Our study is to examine whether autophagy inhibitor chloroquine (CQ) can sensitize esophageal cancer cell line TE-1 to IR. Materials/Methods: Cell viability of TE-1 cells treated with CQ was measured by using MTT assay. Formation and volume of acidic vesicular organelles (AVOs) in living cells after IR alone or IR combined with CQ were monitored by fluorescence staining with Lyso-Tracker Red DND-99/ Hoechst 33258 according to the cytoplasmic fractional volume occupied by AVO. The expression of autophagy-related protein LC3-I and LC3-II were determined by SDS-PAGE and Western blotting. The radiosensitivity of CQ at its IC10 concentration on TE-1 cells and survival TE-1 cells preirradiated with 2 Gy in the treatment with CQ before or after exposure to Co g-radiation was evaluated by clonogenic forming assay, and the radiation biology parameters were estimated from the curve fitted by the single-hit multi-target model [SF Z 1-(-e)]. Results: CQ showed dose-dependent inhibition of TE-1 cell growth and the values of IC50 and IC10 were 72.3 mmol/L and 15.4 mmol/L, respectively. Irradiation markedly induced the expression of LC3 and conversion of LC3-I to LC3-II by irradiated TE-1 cells. Compared with radiation alone and CQ pre-treatment, post-irradiation with addition of CQ significantly reduced accumulation and fluorescence intensity of AVO in surviving progenies of irradiated cells, and clonogenic survival of TE-1 cells and pre-irradiated TE-1 cells and their corresponding D0 (Gy), Dq (Gy) and SERD0 were 1.39, 0.20, 1.44 and 1.15, 0.31, 2.39, respectively. Likewise, pretreatment of pre-irradiated TE-1 cells with CQ significantly reduced clonogenic survival of irradiated cells and their corresponding D0 (Gy), Dq (Gy) and SERD0 were 1.78, 0.24, 1.54, respectively. Conclusions: Our findings suggest that blocking of autophagy would make esophageal cancer cells more sensitive to ionizing radiation and application of CQ could be used as an adjuvant for improving radiation therapy when radio-resistance develops as a result of autophagy response. Author Disclosure: X. Yuan: None. J. Huang: None. X. Zha: None. B. Chen: None. B. Deng: None. T. Li: None.