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目的:探讨肿瘤坏死因子样凋亡微弱诱导剂(TWEAK)在调控上皮性卵巢癌(EOC)细胞对顺铂(DDP)敏感性中发挥的作用。方法:不同浓度TWEAK刺激A2780/cDDP细胞后,采用CCK-8法检测细胞的增殖能力及DDP半数抑制浓度(IC50)的变化;采用流式细胞术检测细胞凋亡率的变化;采用透射电镜检测细胞核染色质形态和凋亡小体的变化;Western blot法检测细胞凋亡相关蛋白caspase 3的活化情况。结果:TWEAK对A2780/cDDP细胞的增殖能力无影响,但能显著增加A2780/cDDP细胞对DDP的敏感性。流式结果显示,随着TWEAK剂量增加,A2780/cDDP细胞的凋亡显著增加。TWEAK刺激后A2780/cDDP细胞中caspase 3活化体表达增加,细胞核染色质发生形态变化,诱导了细胞的凋亡及凋亡小体形成。结论:TWEAK通过活化凋亡相关通路,促进EOC细胞凋亡,提高了DDP耐药EOC细胞对DDP的敏感性。这可能为临床开创逆转EOC铂类耐药的治疗新途径提供理论依据。
Objective: To investigate the role of TWEAK in regulating the sensitivity of epithelial ovarian cancer (EOC) cells to cisplatin (DDP). Methods: A2780 / cDDP cells were stimulated with different concentrations of TWEAK and the cell proliferation and IC50 were measured by CCK-8 assay. The changes of apoptotic rate were detected by flow cytometry. Transmission electron microscopy Nuclear chromatin morphology and apoptotic bodies; Western blot was used to detect the activation of caspase 3. RESULTS: TWEAK had no effect on the proliferation of A2780 / cDDP cells, but significantly increased the sensitivity of A2780 / cDDP cells to DDP. Flow cytometry results showed that the apoptosis of A2780 / cDDP cells was significantly increased with the increase of TWEAK dose. After stimulated with TWEAK, the expression of caspase 3 activator in A2780 / cDDP cells increased, and the morphological changes of nuclear chromatin occurred. The apoptosis and the formation of apoptotic bodies were induced. Conclusion: TWEAK can promote the apoptosis of EOC cells through activating apoptosis-related pathways and increase the sensitivity of DDP-resistant EOC cells to DDP. This may provide a theoretical basis for the clinical development of a new way to reverse the platinum resistance of EOC.