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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 synthesize TMTP1-Dox, a novel anticancer drug, and investigate its potential application in chemotherapy of cervical cancer. Methods: The normal cervical epithelial immortalized cell line End1 and cervical cancer cell lines SiHa and C-33A were selected. Transwell assay to verify invasion and metastasis. Cell Affinity Assay FITC-TMTP1 was tested for its affinity to cell lines. Flow cytometry was used to detect cellular uptake of Dox and TMTP1-Dox. The growth inhibition rates of Dox and TMTP1-Dox on End1, C-33A and SiHa cells were detected by CCK-8 assay. Results: The invasive ability of SiHa cells was significantly stronger than that of C-33A and End1 cells. The affinity of TMTP1 to SiHa cells was higher than that of C-33A and End1. The uptake of TMTP1-Dox by SiHa cells was significantly higher than that of C-33A and End1. The differences were statistically significant (P <0.05). The effect of TMTP1-Dox / Dox on the proliferation of SiHa cells was not significantly different at 12 and 24 h (P <0.05). The effect of TMTP1-Dox on C-33A and End1 cells was significantly weaker than that of Dox cells (P <0.05). Conclusion: TMTP1-Dox selectively inhibits the growth and proliferation of highly invasive cervical cancer cells, and has a low toxic effect on normal cells. Tip TMTP1-Dox for cervical cancer targeted therapy has potential applications.