重组海藻凝集素通过诱导细胞凋亡与自噬抑制宫颈癌细胞增殖

Recombinant Griffithsin Exhibits Highly Inhibitory Activity for Cervical Cancer HeLa Cells by Inducing Apoptosis and Autophagy

目的:探究重组海藻凝集素rGRFT是否具有抗肿瘤活性,并进一步阐明rGRFT的抗癌分子机制。方法:通过"GRFT-linker-GRFT"的形式构建重组GRFT(rGRFT)蛋白,在宫颈癌HeLa细胞、乳腺癌MCF-7细胞、胰腺癌PANC-1细胞和肝癌HepG2细胞分别进行rGRFT的抗肿瘤实验及机制研究。结果:rGRFT对HeLa细胞的增殖抑制作用明显高于其他癌细胞,对人包皮成纤维细胞(HFF)无细胞毒性,且通过诱导HeLa细胞凋亡和自噬发挥抗宫颈癌活性。结论:rGRFT具有抑制宫颈癌HeLa细胞增殖的功能,有望在未来的临床治疗中作为一种新的安全有效的抗宫颈癌药物。

Objective:To explore whether recombinant lectin rGRFT has anti-tumor activity,and investigate the anticancer molecular mechanism of rGRFT.Methods:The rGRFT is generated by expressing its two subunits in"GRFT-linker-GRFT"form in E.coli BL21.The anti-tumor effects of rGRFT are conducted on several cancer cells including cervical cancer HeLa cells,breast cancer MCF-7 cells,pancreatic cancer PANC-1 cells and liver hepatocellular carcinoma HepG2 cells.Results:The rGRFT exhibites more significantly proliferation inhibition on HeLa cells than other cancer cells,and showes no cytotoxicity on normal human foreskin fibroblasts(HFF)cells.The anticancer molecular mechanism of rGRFT is further elucidated by inducing apoptosis and autophagy in HeLa cells.Conclusion:rGRFT endures a new function of inhibiting cervical cancer HeLa cells that may be used as a potent anti-cervical cancer drug in future clinical therapy.