HP-10对结肠癌LoVo细胞体内外增殖的影响

目的通过体内外实验检测六肽分子HP-10的细胞内转导能力和抗LoVo细胞增殖活性。方法MTT法观察75、37.5、18.75μmol/LHP-10对人结肠癌LoVo细胞增殖的影响,运用激光共聚焦显微术和流式细胞仪分别检测HP-10的LoVo细胞内转导能力以及对LoVo细胞周期和凋亡的影响;建立LoVo细胞裸鼠皮下移植瘤模型,验证750、375、75μmol/LHP-10在体内的抗结肠癌生长作用。结果75、37.5、18.75μmol/LHP-10对LoVo细胞体外增殖有明显的抑制作用,且呈剂量依赖性抑制(P<0.05);HP-10能直接跨膜进入LoVo细胞并促进LoVo细胞凋亡发生,但对其周期无明显影响;在结肠癌模型上HP-10能显著地抑制肿瘤生长(P<0.05)。结论HP-10是一种无需穿膜肽引导可直接进入细胞的寡肽,在体内外对LoVo细胞具有明显的抑制生长作用,这种作用是通过诱导细胞凋亡产生的。

Effects of HP-10 on proliferation of human colon adenocarcinoma LoVo cells in vitro and in vivo

Objective To investigate the in vitro and in vivo effects of HP-10, a hexa-peptide β-Ala-Arg-Leu-Arg-Trp-Arg, on the proliferation of human colon adenocarcinoma LoVo cells and the penetration ability of HP-10 into the LoVo cells. Methods MTT assays were used to identify the effects of HP-10 on the LoVo cells at 75, 37.5 or 18.75 μmol/L. The membrane permeable effect of HP-10, the cell cycle and apoptosis were determined by confocal laser fluorescence microscopy and flow cytometry respectively. Then the model of colon cancer of nude mice was established with implantation of LoVo cells (3×10~6) and the therapeutic effect of HP-10 at concentrations of 750, 375 and 75 μmol/L respectively was observed. Results HP-10 markedly inhibited the proliferation of LoVo cells in a dose-dependent manner (P<0.05). HP-10 was able to transduce directly into LoVo cells and further induce cell apoptosis (P<0.05), but had no effect on cell cycle (P>0.05). Moreover, the growth of tumors was inhibited obviously by HP-10 in this adenocarcinoma model (P<0.05). Conclusion HP-10 is an oligopeptide able to directly transduce into cells without the coupling cell-penetrating peptide. It can inhibit the growth of LoVo cells in vitro and in vivo through inducing cell apoptosis.