奥拉帕尼对人非小细胞肺癌细胞增殖及辐射敏感性的影响

Effect of Olaparib on proliferation activity and radiosensitization of human non-small cell lung cancer cells

目的 探讨聚腺苷二磷酸核糖聚合酶(PARP)抑制剂奥拉帕尼对人非小细胞肺癌细胞增殖及辐射敏感性的影响.方法 体外培养人非小细胞肺癌H460和H1299细胞,取对数生长期细胞进行实验.采用噻唑蓝(MTT)实验测定奥拉帕尼对H460和H1299细胞增殖的影响,克隆形成实验检测奥拉帕尼对H460和H1299细胞辐射敏感性的影响,彗星实验检测奥拉帕尼对H460和H1299细胞辐射诱导DNA损伤的影响.结果 MTT实验结果表明奥拉帕尼能显著抑制H460和H1299细胞的增殖(均P<0.05),且H1299细胞对奥拉帕尼更敏感.克隆形成实验结果表明奥拉帕尼能显著增强H460和H1299细胞的辐射敏感性(均P<0.05).彗星实验结果表明奥拉帕尼联合γ射线照射能显著提高H460和H1299细胞的DNA损伤水平.结论 奥拉帕尼能增强人非小细胞肺癌细胞的辐射敏感性,且奥拉帕尼的辐射增敏作用可能与其抑制细胞增殖、增强电离辐射诱导的DNA损伤有关.

Objective To investigate the effects of Olaparib on cell proliferation and radiosensitization of human non-small cell lung cancer cells.Methods Non-small cell lung H460 and H1299 cell lines were cultured in vitro and the cells in logarithmic growth phase were selected for experiments.MTT and colony formation assays were used to determine cell proliferation and radiosensitization,respectively.Single cell gel electrophoresis assay (comet assay) was used to detect irradiation-induced DNA damage.Results The results of MTT assay showed that Olaparib inhibited the proliferation of H460 and H1299 cells in a dose-dependent pattern (all P<0.05).H1299 cell line was more sensitive to Olaparib than H460 cells.The results of colony formation assay showed that Olaparib enhanced the radiosensitizition of H460 and H1299 cells (all P<0.05).The results of comet assay showed that Olaparib increased γ ray-induced DNA damage.Conclusions Olapani can enhance the radiosensitization of human non-small cell lung cancer cells,and the radiosensitization effect of Olaparib may be associated with the inhibition of cell proliferation and induction of irradiation-induced DNA damage.