姜黄素增强人乳头瘤状甲状腺癌细胞TP C-1放射敏感性的研究

摘要

目的：研究姜黄素对人乳头瘤状甲状腺癌细胞TCP⁃1放射敏感性的影响，并探索姜黄素可能作用的信号通路，为甲状腺癌放射增敏剂的开发提供新的思路。方法使用姜黄素和放射性碘处理人乳头瘤状甲状腺癌细胞TPC⁃1，CCK⁃8法检测细胞增殖，克隆形成实验检测细胞克隆形成能力，流式细胞仪检测细胞凋亡情况， western blot检测p50、p65、凋亡相关蛋白Bcl⁃2和Bax的表达变化。使用NF⁃κB信号通路抑制剂PDTC抑制NF⁃κB信号通路活性，检测细胞增殖、克隆形成和凋亡变化。结果姜黄素和放射性碘处理人乳头瘤状甲状腺癌细胞TPC⁃1后，细胞增殖率下降，克隆形成减少，凋亡上升，凋亡抑制蛋白Bcl⁃2表达下调，促凋亡蛋白Bax表达上调，并呈浓度依赖性。这些结果表明姜黄素可增加TPC⁃1细胞的放射敏感性。碘放射后TPC⁃1细胞NF⁃κB通路活化，姜黄素可以抑制碘放射后TPC⁃1细胞NF⁃κB通路的激活。使用抑制剂抑制NF⁃κB通路的活性，细胞增殖下降，克隆形成减少，凋亡上升，放射敏感性升高。结论姜黄素可能靶向NF⁃κB信号通路，通过抑制NF⁃κB信号通路活性调节甲状腺癌细胞的放射敏感性。%Objective To study the effect of curcumin on the radiosensitivity of the human papillary thyroid cancer cell line TPC⁃1, to investigate the signaling pathway probably targeted by curcumin, and to provide new insights for the development of radiosensitizers for thyroid cancer. Methods The human papillary thyroid cancer cell line TPC⁃1 was treated with curcumin and radioactive iodine. CCK⁃8 assay, colony formation assay, and flow cytometry were used to evaluate cell proliferation, colony formation ability, and cell apoptosis, respectively. Western blot was used to measure the expression of p50, p65, and apoptosis⁃related proteins, Bcl⁃2 and Bax. Cell proliferation, colony formation ability, and cell apoptosis were determined again after the activity of the NF⁃κB signaling pathway was blocked by a NF⁃κB signaling pathway inhibitor PDTC. Results After treatment with curcumin and radioactive iodine, the human papillary thyroid cancer TPC⁃1 cells had reduced cell proliferation and colony formation, an elevated apoptosis rate, downregulated expression of anti⁃apoptotic Bcl⁃2, and upregulated expression of pro⁃apoptotic Bax in a dose⁃dependent manner. These results indicated that curcumin enhanced the radiosensitivity of TPC⁃1 cells. Curcumin inhibited the activation of the NF⁃κB signaling pathway in the TPC⁃1 cells treated with radioactive iodine. When the activity of the NF⁃κB pathway was blocked by PDTC, cell proliferation and colony formation were reduced and the apoptosis rate was increased, indicating an enhanced radiosensitivity of TPC⁃1 cells. Conclusions Curcumin is likely to target the NF⁃κB signaling pathway. It regulates the radiosensitivity of thyroid cancer cells by inhibiting the activity of the NF⁃κB signaling pathway.