肿瘤靶向多肽TMTP1偶联阿霉素选择性地抑制高侵袭性宫颈癌细胞株生长的体外研究  

The selective anti-tumor effects of the TMTP1-Doxorubicin conjugates on cervical cancers cell lines

作　　者：张振中 魏睿 李飞 吕梦琴 丁惠[1] 奚玲[2] 罗丹枫 Zhang Zhenzhong Wei Rui Li Fei et al(Department of Gynecologic Oncology,Henan Cancer Hospital, Zhengzhou 450008 Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College ,Huazhong University of Science and Technology, Wuhan 430030)

机构地区：[1]河南省肿瘤医院妇科肿瘤,郑州450008 [2]华中科技大学同济医学院附属同济医院妇产科,武汉430030

出　　处：《现代妇产科进展》2017年第9期651-655,共5页Progress in Obstetrics and Gynecology

基　　金：国家自然科学基金资助项目(No:81202061);国家自然科学基金面上项目(No:81472444)

摘　　要：目的:合成一种新型的抗肿瘤药物TMTP1-Dox,探讨其应用于宫颈癌化疗的潜在应用价值。方法:选取正常宫颈上皮永生化细胞系End1及宫颈癌细胞系SiHa和C-33A。Transwell试验验证侵袭转移能力。细胞亲和试验检测FITC-TMTP1对细胞株的亲和能力。流式细胞仪检测Dox及TMTP1-Dox的细胞摄入。CCK-8法检测Dox和TMTP1-Dox作用于End1、C-33A和SiHa细胞时的生长抑制率。结果:SiHa细胞的侵袭能力显著强于C-33A和End1细胞,TMTP1对SiHa细胞的亲和力高于C-33A和End1,SiHa细胞对TMTP1-Dox的摄入量显著多于C-33A和End1,差异均有统计学意义(P<0.05)。作用12和24h时,TMTP1-Dox/Dox对SiHa细胞的生长抑制率无显著差异(P<0.05)。TMTP1-Dox对C-33A和End1细胞的生长抑制作用明显弱于Dox细胞,差异有统计学意义(P<0.05)。结论:TMTP1-Dox能选择性地抑制高侵袭能力的宫颈癌细胞的生长增殖,对正常细胞的毒性作用低。提示TMTP1-Dox对于宫颈癌的靶向治疗具有潜在应用价值。Objective：To investigate the specificity and anti-tumor ability of the TMTP1-Doxorubicin conjugates（TMTP1-Dox） on highly invasive cervical cancer cells in vitro.Methods：The immortalized cervical epithelial cell End1 and cervical cancer cells SiHa,C-33A which had different invasive capacities were used.The cell invasion was investigated using the Transwell system.FITC-conjugated TMTP1 was used to determine the specific binding in abovementioned cell lines.The uptakes of Doxorubicin and TMTP1-Doxorubicin in those cells were measured by flow cytometry.The viability of SiHa,C-33A and End1 cells after treatment with Dox and TMTP1-Dox at IC（50） concentrations for 12,24,48 and 72 h were measured by CCK-8 assay respectively.Result：The invasive capability of SiHa was higher than C-33A and End1,and Siha also took more significant amount of TMTP1-Dox among those cells which corresponded to its specifical binding to FITC-TMTP1.CCK-8 assay indicated that the inhibit rate of TMTP1-Dox were significantly lower in C-33A and End1 cells,comparing with Dox.There was no obvious difference between the treatment with Dox and TMTP1-Dox in SiHa for 12,24 h respectively.Conclusions：TMTP1-Dox can inhibit the proliferation of highly invasive cervical cancer cell SiHa,while it has little effect in C-33A and End1.TMTP1-Dox may be a powerful candidate therapeutic agent for cervical cancer.

关 键 词：靶向多肽 阿霉素 宫颈癌 侵袭 

分 类 号：R737.33[医药卫生—肿瘤]