基质金属蛋白酶组织抑制因子基因高表达可增加宫颈癌细胞放疗敏感性  

High expression of tissue inhibitor of metalloproteinases-3 gene sensitizes HPV positive cervical cancer cells to irradiation in vitro.

作　　者：魏华莉[1,2] 张颖[3] 杨隽钧[1] 张雪燕[4] 付明[4] 梁萧[4] 段华[3] 林晨[4] 向阳[1] 

机构地区：[1]中国医学科学院中国协和医科大学北京协和医院妇产科,北京100730 [2]煤炭总医院妇产科,北京100028 [3]北京妇产医院,北京100006 [4]中国医学科学院肿瘤研究所,北京100021

出　　处：《中国实用妇科与产科杂志》2010年第7期521-524,共4页Chinese Journal of Practical Gynecology and Obstetrics

基　　金：国家自然科学基金青年项目(C03030401);北京市科技新星课题(2006B09)

摘　　要：目的探讨携带基质金属蛋白酶组织抑制因子-3(TIMP-3)基因的重组腺病毒(Ad-TIMP-3)在体外对人乳头瘤病毒(HPV)阳性宫颈癌细胞的作用以及与放疗联合应用的效果。方法 2008年10月至2009年4月采用RT-PCR法和Western Blot法检测感染Ad-TIMP-3的HeLa-Luc与CaSki细胞表达TIMP-3 mRNA及蛋白质水平;MTT法检测Ad-TIMP-3对HeLa-Luc和CaSki细胞增殖的抑制作用;平板克隆形成、细胞黏附性及侵袭性实验检测受X射线辐射细胞生长、黏附性和侵袭的能力。结果感染Ad-TIMP-3后,HeLa-Luc和CaSki细胞表达TIMP-3水平明显升高。Ad-TIMP-3能够明显抑制HeLa-Luc和CaSki细胞增殖,且具有剂量效应关系。Ad-TIMP-3与X射线联合应用可显著减少HeLa-Luc和CaSki细胞平板克隆形成数(P<0.01),显著减弱宫颈癌细胞的侵袭能力及黏附性(P<0.001)。结论 Ad-TIMP-3具有抑制宫颈癌细胞增殖的能力;与X射线联合应用后,Ad-TIMP-3显著提高宫颈癌细胞对放射治疗的敏感性。Objective To explore the effects of adenovirus delivered tissue inhibitor of metalloproteinases-3 （ Ad-TIMP- 3） on HPV positive cervical cancer cell lines and to study whether exogenous TIMP-3 sensitizes HPV positive cervical cancer cells to irradiation in vitro. Methods We measured the expression of TIMP-3 mRNA by RT-PCR and TIMP-3 protein by Western Blot in CaSki and HeLa-Luc cells after transfered Ad-TIMP-3. We measured the growth inhibition of CaSki and HeLa-Luc cells after transfered Ad-TIMP-3 by MTT. An adenovirus expressing TIMP-3 （ Ad-TIMP-3）, alone or in combination with irradiation, was used to treat HPV positive cervical cancer cells HeLa Luc and CaSki ,we compared the growth inhibition efficacy,invasion and adhesion ability. Results RT-PCR and Western Blot revealed that the ex- pression of exogenous TIMP-3 was elevated obviously after infection. Ad-TIMP-3 suppressed the growth of HPV positive cervical cancer cells. Combination of Ad-TIMP-3 and irradiation significantly decreased the clone numbers（ P 〈 0. 01 ）, the invasion and adhesion ability（P 〈0. 001 ）. Conclusion Ad-TIMP-3 suppresses the HeLa - Luc and CaSki cells＇ growth and sensitizes HPV positive cervical cancer cells to irradiation in vitro. Combination of Ad-TIMP-3 and x-ray is a potential novel approach to the therapy of HPV positive cervical cancer.

关 键 词：基因治疗 基质金属蛋白酶组织抑制因子-3 腺病毒 宫颈癌 放疗敏感性 

分 类 号：R71[医药卫生—妇产科学]