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目的:观察姜黄素与顺铂协同对T24膀胱癌细胞的抑制作用,并探讨姜黄素能否下调肿瘤细胞的抗化疗Keap1-Nrf2通路。方法:用不同浓度姜黄素(5、10、20μmol/L)联合顺铂(30μg/m L)处理T24细胞24 h后,MTT法测定姜黄素联合顺铂对T24细胞增殖的抑制作用;Western blotting检测T24细胞核内Nrf2、Keap1的蛋白水平,细胞浆内Keap1的蛋白水平以及二相抗毒酶GSTP1、NQO1水平。结果:不同浓度姜黄素联合顺铂呈剂量依赖性抑制T24细胞的增殖;姜黄素可显著降低T24细胞核内Nrf2蛋白水平但增加核内Keap1的蛋白水平;并可显著降低胞浆内二相抗毒酶GSTP1、NQO1水平。结论:姜黄素与顺铂可协同抑制T24膀胱癌细胞的增殖,其机制可能与下调肿瘤细胞的Keap1-Nrf2通路,使T24细胞内Nrf2介导的二相抗毒酶的表达降低,从而增强肿瘤细胞对化疗药物的敏感性有关。
Objective: To observe the inhibitory effect of curcumin and cisplatin on T24 bladder cancer cells and to explore whether curcumin can down-regulate the chemotherapeutic Keap1-Nrf2 pathway in tumor cells. Methods: T24 cells were treated with different concentrations of curcumin (5, 10, 20μmol / L) and cisplatin (30μg / mL) for 24 h. The inhibitory effects of curcumin and cisplatin on the proliferation of T24 cells were determined by MTT assay. The protein levels of Nrf2 and Keap1, the protein level of Keap1 in cytoplasm, and the levels of GSTP1 and NQO1 were detected. Results: Curcumin combined with cisplatin inhibited the proliferation of T24 cells in a dose-dependent manner. Curcumin significantly reduced the level of Nrf2 protein in nuclear of T24 cells but increased the protein level of Keap1 in nucleus. Enzyme GSTP1, NQO1 levels. CONCLUSION: Curcumin and cisplatin can synergistically inhibit the proliferation of T24 bladder cancer cells. The mechanism may be related to down-regulating the Keap1-Nrf2 pathway in tumor cells and reducing the expression of Nrf2-mediated two-phase antitumor enzyme in T24 cells, Cell sensitivity to chemotherapeutic drugs.