摘要
目的 探讨肿瘤坏死因子受体相关蛋白1(TRAP1)在顺铂耐药性卵巢癌中的表达以及对顺铂耐药性卵巢癌细胞氧化磷酸化的影响。方法 收集2019-01-10-2020-01-10郑州人民医院手术切除的卵巢癌组织样本41例,其中顺铂敏感26例(顺铂敏感组),顺铂耐药15例(顺铂耐药组),癌旁组织10例(对照组),及细胞株A2780与顺铂耐药株A2780CP,测定上述对象中TRAP1表达。通过转染siRNA沉默A2780CP细胞中TRAP1表达,检测细胞全细胞及线粒体耗氧率(OCR)、ATP产量变化,检测加药顺铂时细胞增殖活性和凋亡率的变化。结果 顺铂耐药组、顺铂敏感组和对照组TRAP1蛋白表达水平分别为1.00±0.30、0.60±0.14和0.22±0.08,差异有统计学意义,F=47.640,P<0.001。A2780CP细胞TRAP1蛋白表达水平(2.24±0.10)高于A2780细胞(1.00±0.05),差异有统计学意义,t=11.383,P=0.001。与A2780细胞相比,A2780CP细胞的顺铂IC50浓度升高,全细胞及线粒体OCR、ATP产量均升高,差异有统计学意义,t值分别为3.429、4.519和3.369,P值分别为0.006、0.001和0.007;与A2780CP-si-NC组相比,转染TRAP1 siRNA后A2780CP细胞全细胞及线粒体OCR、ATP产量减少,t值分别为3.180、2.340和3.097,P值分别为0.010、0.041和0.011;细胞增殖活性降低,F=147.957,P<0.001;凋亡率升高,F=113.279,P<0.001。结论 TRAP1在卵巢癌耐药组织中高表达,可能通过调控氧化磷酸化参与卵巢癌的顺铂耐药过程。
Objective To investigate the expression of tumor necrosis factor receptor-associated protein 1(TRAP1) in cisplatin-resistant ovarian cancer and its effect on oxidative phosphorylation in cisplatin-resistant ovarian cancer cells.Methods Forty-one ovarian cancer tissue samples were collected from Zhengzhou People’s Hospital between January 10,2019 and January 10,2020 and divided into the cisplatin sensitive group(26 cases, cisplatin-sensitive group) and cisplatin resistant group(15 cases, cisplatin-resistant group) according to the follow-up results after chemotherapy.Meanwhile, adjacent tissues were collected as control group(10 cases, control group).The expression of TRAP1 in tissues in each groups, A2780 and cisplatin-resistant cells A2780CP were detected;The expression of TRAP1 in A2780CP cells was silenced by siRNA transfection.The changes of oxygen consumption rate(OCR) in whole cells and mitochondria, ATP production, the proliferation activity and the apoptosis rate under cisplatin were detected.Results The expression of TRAP1 protein in the cisplatin-resistant group, cisplatin-sensitive group and control group was 1.00±0.30,0.60±0.14,0.22±0.08,and the difference was significant, F=47.640,P<0.001.The expression of TRAP1 in A2780CP cells(2.24±0.10) was higher than that in A2780 cells(1.00±0.05),and the difference was significant, t=11.383,P=0.001;Compared with A2780 cells, IC50concentration of cisplatin in A2780CP cells was increased, and the OCR of whole cell and mitochondria, ATP production in A2780CP cells were significantly increased, while the apoptosis rate under cisplatin was decreased, and the differences were statistically significant(t=3.429,P=0.006;t=4.519,P=0.001;t=3.369,P=0.007);Compared with the A2780CP-si-NC group, the OCR of whole cell and mitochondria, ATP production and the proliferation activity of A2780CP cells transfected with TRAP1siRNA were significantly decreased,and the apoptosis rate under cisplatin was increased,the differences were statistically significant(t=3.180,P=0.010;t
作者
胡颜霞
宋晓霞
张喜红
HU Yanxia;SONG Xiaoxia;ZHANG Xihong(Department of Gynecology,Zhengzhou People's Hospital,Zhengzhou 450052,China)
出处
《中华肿瘤防治杂志》
CAS
北大核心
2023年第4期205-212,共8页
Chinese Journal of Cancer Prevention and Treatment
基金
河南省社会发展领域科技攻关项目(162102310233)
河南省科技攻关计划(222102310488)。
关键词
肿瘤坏死因子受体相关蛋白1
卵巢癌
顺铂
耐药
氧化磷酸化
tumor necrosis factor receptor-associated protein 1
ovarian cancer
cisplatin
drug resistant
oxidative phosphorylation
