PDCD5因子增强顺铂抑制结肠癌细胞生长作用的体内研究

Programmed cell death 5 enhance inhibitory effect of cisplatin on growth of colorec- tal carcinoma cells in vivo

目的通过体内实验研究稳定转染程序性细胞死亡5(PDCD5)因子的结肠癌细胞对顺铂的敏感性,探讨PDCD5因子与顺铂联合治疗结肠癌的可行性。方法稳定转染PDCD5因子的结肠癌细胞SW480/PDCD5、稳定转染空载体的结肠癌细胞SW480/Neo及正常结肠癌细胞SW480分别接种到裸鼠皮下,形成皮下移植瘤后,顺铂(10 mg/kg)腹腔内注射,绘制移植瘤生长曲线;组织学观察皮下移植瘤,TUNEL法检测皮下移植瘤的凋亡情况;Western印迹法检测皮下移植瘤caspase-9和caspase-3的表达水平。结果 SW480/PDCD5对顺铂更加敏感,肿瘤体积增加幅度低于SW480和SW480/Neo(P<0.05);SW480/PDCD5有更多的细胞出现变性坏死,更多的细胞染色体边集并出现凋亡小体,出现凋亡细胞的比例高于SW480和SW480/Neo(P<0.05);SW480/PDCD5中caspase-9和caspase-3的活化片段较SW480和SW480/Neo更多(P<0.05)。结论稳定转染PDCD5因子可以增加结肠癌细胞对顺铂的敏感性,二者联合应用在结肠癌治疗中有潜在的价值。

Objective To investigate the inhibitory effects of Programmed cell death 5 （PDCD5） in combination with cisplatin on colorectal carcinoma cells in vivo. Methods Colorectal cancer cells of SW480, SW480/Neo and SW480/PDCD5 were subcutaneously inoculated into the nude mice, and cisplatin （10 mg/kg） was administrated via in- traperitoneal injection. Histologic apoptosis analysis and tumor growth curves of colorectal cancer xenografl model were accomplished. Caspase-9 and caspase-3 were determined by Western blotting. Results Compared with SW480 and SW480/Neo, SW480/PDCD5 was more sensitive to cisplatin, and its tumor volume increased smaller （P 〈 0.05）. Combination of PDCD5 and cisplatin caused obviously cell death in tumor mass via apoptosis （P 〈 0.05 ）. Compared with SW480 and SW480/Neo, SW480/PDCD5 showed more cleaved caspase-9 and caspase-3 （P 〈 0.05）. Conclusion Stable overexpression of PDCD5 increases sensitivity of the cells to cisplatin, PDCD5 therapy in combination with cis- platin could be promising alternative in colorectal cancer treatment.