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

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.