Huang Zhi, Zhang Shuai, Shen Yaping, Liu Weixin, Long Jipu, Zhou Shi
Department of Interventional Radiology, The Affiliated Baiyun Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, People's Republic of China.
Department of Interventional Radiology, Cancer Hospital of Guizhou Medical University, Guiyang, People's Republic of China.
Ther Clin Risk Manag. 2016 Feb 15;12:217-23. doi: 10.2147/TCRM.S95453. eCollection 2016.
Multi-drug resistance (MDR) is the main cause of tumor failure to chemotherapy. This study aims to explore the influence of MDR1 methylation on curative effect of interventional embolism chemotherapy for cervical cancer.
Sixty-seven patients with cervical cancer receiving embolism chemotherapy were selected, and 45 normal cervical tissues were included as a control. Immunohistochemistry was used to detect the level of P-glycoprotein (P-gp) in cervical cancer, and to make an analysis compared with normal tissues. The methylation status of the MDR1 gene promoter region 16 CpG units was analyzed by using kilobase-specific cracking and matrix-assisted laser desorption ionization time of flight mass spectrometry.
The results indicated that the positive expression rates of P-gp were 0% (0/45) in normal cervical tissue, and 61.19% (41/67) and 77.61% (52/67) before and after interventional embolism chemotherapy in cervical cancer tissues, respectively. There were significant differences compared with normal cervical tissues (χ (2)=4.2523, 0.0392). The positive expression rate of P-gp before chemotherapy was negatively correlated with efficacy of chemotherapy (r=-0.340, P=0.005). Methylation rate of 13 CpG units in normal tissues was significantly greater than cervical tissues (P<0.05). In cervical cancer tissue, methylation rate of six CpG units before interventional embolism chemotherapy was higher than after chemotherapy, but that of one CpG unit was lower than after chemotherapy (P<0.05). The methylation rate of one CpG unit with effective chemotherapy before chemotherapy was significantly higher than ineffective chemotherapy (P<0.05), and the other CpG units were similar (P>0.05).
P-gp expression level coded by MDR1, methylation status of partial MDR1 gene promoter regions CpG island, is closely related to the efficacy of interventional embolism chemotherapy for cervical cancer before the operation.
多药耐药（MDR）是肿瘤化疗失败的主要原因。本研究旨在探讨MDR1甲基化对宫颈癌介入栓塞化疗疗效的影响。
选取67例接受栓塞化疗的宫颈癌患者，并纳入45例正常宫颈组织作为对照。采用免疫组织化学法检测宫颈癌组织中P-糖蛋白（P-gp）水平，并与正常组织进行比较分析。利用千碱基特异性裂解和基质辅助激光解吸电离飞行时间质谱分析MDR1基因启动子区16个CpG单位的甲基化状态。
结果表明，正常宫颈组织中P-gp阳性表达率为0%（0/45），宫颈癌组织介入栓塞化疗前后P-gp阳性表达率分别为61.19%（41/67）和77.61%（52/67）。与正常宫颈组织相比差异有统计学意义（χ²=4.2523，P=0.0392）。化疗前P-gp阳性表达率与化疗疗效呈负相关（r=-0.340，P=0.005）。正常组织中13个CpG单位的甲基化率显著高于宫颈组织（P<0.05）。在宫颈癌组织中，介入栓塞化疗前6个CpG单位的甲基化率高于化疗后，但1个CpG单位的甲基化率低于化疗后（P<0.05）。化疗前化疗有效的1个CpG单位的甲基化率显著高于化疗无效者（P<0.05），其他CpG单位相似（P>0.0
