PXR、MDR1、CYP3A5和CYP2B6在高级别浆液性卵巢癌组织中的表达及其意义  

EXPRESSION OF PXR,MDR1,CYP3A5,AND CYP2B6 IN HIGH-GRADE SEROUS OVARIAN CANCER AND ITS SIGNIFICANCE

作　　者：张萍[1] 马岚 陈桦[3] ZHANG Ping;MA Lan;CHEN Hua(School of Basic Medicine,Qingdao University,Qingdao 266071,China)

机构地区：[1]青岛大学基础医学院,山东青岛266071 [2]临沂市平邑县中医院病理科 [3]青岛市市立医院病理科

出　　处：《精准医学杂志》2023年第2期135-139,144,共6页Journal of Precision Medicine

摘　　要：目的探讨孕烷X受体(PXR)、多药耐药蛋白1(MDR1)、细胞色素P4503A5(CYP3A5)和细胞色素P4502B6(CYP2B6)在高级别浆液性卵巢癌(high grade serous ovarian cancer,HGSOC)组织中的表达及其意义。方法选取2019年9月-2021年12月青岛市市立医院妇科收治的56例HGSOC患者作为试验组,据其对铂类药物的耐药情况分为耐药组(24例)和敏感组(32例),另外选取妇科同期收治的16例子宫肌瘤患者作为对照组。采用免疫组织化学、实时定量荧光PCR及蛋白印迹法对试验组患者HGSOC组织和对照组患者正常输卵管组织中PXR、MDR1、CYP3A5和CYP2B6的表达情况进行检测。结果与对照组相比较,试验组患者PXR、MDR1、CYP3A5、CYP2B6阳性表达率显著升高(χ^(2)=12.879~17.174,P<0.05),mRNA相对表达量显著升高(t=9.746~17.640,P<0.05),蛋白表达量显著升高(t=13.312~60.448,P<0.05);与敏感组相比,耐药组患者PXR、MDR1、CYP3A5、CYP2B6阳性表达率显著升高(χ^(2)=4.371~8.549,P<0.05),mRNA相对表达量显著升高(t=6.859~19.000,P<0.05),蛋白表达量显著升高(t=8.693~27.670,P<0.05)。HGSOC患者PXR与CYP3A5、CYP2B6的表达呈正相关(r=0.332、0.308,P<0.05),与MDR1的表达无明显相关性(P>0.05)。结论PXR、MDR1、CYP3A5、CYP2B6在HGSOC患者的肿瘤组织中呈高表达,其可能参与HGSOC的发生发展过程。PXR、MDR1、CYP3A5和CYP2B6的表达检测可用于判断HGSOC对化疗的敏感性,有助于为术后化疗提供指导意见。Objective To investigate the expression and significance of progesterone X receptor(PXR),multidrug resistant protein 1(MDR1),cytochrome P4503A5(CYP3A5),and cytochrome P4502B6(CYP2B6)in high-grade serous ovarian cancer(HGSOC).Methods A total of 56 patients with HGSOC admitted to the Department of Gynecology,Qingdao Municipal Hospital from September 2019 to December 2021 were included in the experimental group.The patients were further divided into drug resistant group(24 cases)and sensitive group(32 cases)according to their resistance to platinum chemotherapy drugs.The control group included 16 patients with uterine fibroids admitted during the same period.The expression of PXR,MDR1,CYP3A5,and CYP2B6 in HGSOC and normal fallopian tubes were determined by immunohistochemistry,real-time quantitative PCR,and Western blotting.Results Compared with the control group,the positive expression rates of PXR,MDR1,CYP3A5,and CYP2B6 were significantly increased in the experimental group(χ^(2)=12.879-17.174,P<0.05),their relative expression of mRNA was significantly increased(t=9.746-17.640,P<0.05),and their protein expression was significantly increased(t=13.312-60.448,P<0.05).Compared with the sensitive group,the positive expression rates of PXR,MDR1,CYP3A5,and CYP2B6 were significantly increased in the drug-resistant group(χ^(2)=4.371-8.549,P<0.05),their relative expression of mRNA was significantly increased(t=6.859-19.000,P<0.05),and their protein expression was significantly increased(t=8.693-27.670,P<0.05).In HGSOC patients,PXR expression was positively correlated with CYP3A5 and CYP2B6(r=0.332,0.308,P<0.05),but had no significant correlation with MDR1(P>0.05).Conclusion PXR,MDR1,CYP3A5,and CYP2B6 are highly expressed in HGSOC,which may be involved in its occurrence and development.The detection of PXR,MDR1,CYP3A5,and CYP2B6 expression can be used to determine the sensitivity of HGSOC to chemotherapy,which is helpful to provide guidance for postoperative chemotherapy.

关 键 词：高级别浆液性卵巢癌 PXR MDR1 CYP3A5 CYP2B6 多药耐药 化疗耐药 

分 类 号：R737.3[医药卫生—肿瘤]