文章摘要

ATP7B功能活性及其基因多态性与绝经后卵巢癌顺铂-紫杉醇化疗耐药相关

作者: 1鲁 振雯, 1朱 红斌, 2丁 晓虎, 2王 席
1 南通大学附属东台医院内分泌科,江苏 盐城 224200
2 南通大学附属东台医院药学科,江苏 盐城 224200
通讯: 王 席 Email: wangxizxmc@163.com
DOI: 10.3978/j.issn.2095-6959.2019.09.017

摘要

目的:探究ATP7B功能活性及其基因多态性与绝经后卵巢癌顺铂-紫杉醇化疗耐药的相关性。方法:在南通大学附属东台医院妇产科和标本库分别采集100例使用顺铂-紫杉醇联合化疗的绝经后卵巢癌患者全血样本,3例绝经后卵巢癌与3例绝经后无原发性卵巢癌患者的卵巢组织样本,按照耐药情况分为化疗敏感组和化疗耐药组。使用RT-PCR和Western印迹技术测定卵巢癌患者和无原发性卵巢癌患者ATP7B的mRNA和蛋白的表达水平,使用PCR-RFLP技术检测绝经后卵巢癌患者ATP7B(rs1061472和rs1801249)位点在化疗敏感组和化疗耐药组基因型频率分布情况。两组临床样本数据采用独立样本t检验和卡方检验进行数据分析。结果:与化疗敏感组相比,化疗耐药组ATP7B mRNA和蛋白表达水平显著升高(P<0.05);两组ATP7B rs1061472和rs1801249位点各基因型频率分布差异有统计学意义(P<0.05)。结论:化疗耐药组绝经后卵巢癌患者ATP7B mRNA的过表达与顺铂-紫杉醇联合化疗耐药情况的发生密切相关。ATP7B rs1061472和rs1801249基因多态性与绝经后卵巢癌患者顺铂-紫杉醇联合化疗耐药显著相关。
关键词: 顺铂-紫杉醇;绝经后卵巢癌;耐药;ATP7B;基因多态性

Functional activity of ATP7B and its gene polymorphisms associate with chemoresistance of cisplatin-paclitaxel in postmenopausal ovarian cancer

Authors: 1LU Zhenwen, 1ZHU Hongbin, 2DING Xiaohu, 2WANG Xi
1 Department of Endocrinology, Affiliated Dongtai Hospital of Nantong University, Yancheng Jiangsu 224200, China
2 Department of Pharmacy, Affiliated Dongtai Hospital of Nantong University, Yancheng Jiangsu 224200, China

CorrespondingAuthor:WANG Xi Email: wangxizxmc@163.com

Abstract

Objective: To investigate ATP7B functional activity and its genetic polymorphisms and postmenopausal ovarian cancer cisplatin-paclitaxel chemotherapy. Correlation of resistance. Methods: One hundred cases of postmenopausal ovarian cancer patients with cisplatin-paclitaxel combined with chemotherapy and 3 cases of postmenopausal ovarian cancer and 3 cases of postmenopausal patients without primary ovarian cancer were collected in our hospital. Ovarian tissue samples were divided into chemotherapy-sensitive group and chemotherapy-resistant group according to drug resistance. RT-PCR and Western Blotting were used to detect the expression of ATP7B mRNA and protein in ovarian cancer patients and patients without primary ovarian cancer. PCR-RFLP was used to detect ATP7B (rs1061472 and rs1801249) sites in postmenopausal ovarian cancer patients. The frequency distribution of genotypes in the sensitive group and the chemoresistance group. The clinical sample data of the two groups were analyzed by independent sample t-test and chi-square test. Results: Compared with the chemotherapy-sensitive group, the mRNA and protein expression levels of ATP7B in the chemotherapy-resistant group were significantly increased. The frequencies of ATP7B rs1061472 and rs1801249 were genotype frequencies in the chemotherapy-sensitive group and ovarian cancer patients in the chemotherapy-resistant group. There was a significant difference in the distribution (P<0.05). Conclusion: The overexpression of ATP7B mRNA in postmenopausal ovarian cancer patients in chemotherapy-resistant group is closely related to the occurrence of cisplatin-paclitaxel combined with chemotherapy. ATP7B rs1061472 and rs1801249 gene polymorphisms were significantly associated with cisplatin-paclitaxel combined chemotherapy resistance in postmenopausal ovarian cancer patients.
Keywords: cisplatin-paclitaxel; postmenopausal ovarian cancer; drug resistance; ATP7B; gene polymorphism