阿司匹林抑制肝癌生长的实验研究

目的探讨阿司匹林对人肝癌生长的影响及是否能诱导其凋亡. 方法用3H-TdR掺入、形态学观察、DNA末端原位标记法(Tunel)和流式细胞术等方法研究阿司匹林对人肝癌细胞株SMMC-7721生长及诱导凋亡的作用;建立人肝癌裸鼠原位移植瘤模型,观察阿司匹林对肝癌移植瘤生长的影响. 结果阿司匹林能显著抑制人肝癌细胞株SMMC-7721生长,当其浓度在1×10-1～1×10-7mol/L时,肝癌细胞3H-TdR掺入与浓度增加呈显著负相关(r＝-0.918,P＜0.01).经1×10-3mol/L阿司匹林作用后可见较多肝癌细胞呈典型的细胞凋亡形态学变化,凋亡指数为(8.90±1.32)%,对照组为 (0.50±0.35)%,两组比较,差异有显著性,流式细胞术也检测到其G1期前有一典型的亚二倍体凋亡峰,凋亡率为 12.79%.阿司匹林能显著抑制人肝癌裸鼠原位移植瘤生长,抑瘤率为71.62%,实验中裸鼠存活率为100%,未见消化道出血、溃疡等不良反应. 结论阿司匹林能显著抑制人肝癌生长并能诱导其凋亡.

Inhibiting effects of aspirin on the growth of human hepatocellular carcinoma

OBJECTIVE: To assess the effects of aspirin on the proliferation and apoptosis of human HCC cells. METHODS: The effects of aspirin on the synthesis of DNA in SMMC-7721 HCC cells were determined by using (3)H-thymidine incorporation. Apoptosis of SMMC-7721 was studied by observation of morphologic changes, Tunnel method and flow cytometry after treatment with aspirin. We also assessed the effects of aspirin on the growth of HCC xenografts in nude mice in vivo. RESULTS: A dose-dependent suppression (r=-0.918, P<0.01) of (3)H-TdR incorporation in HCC cell line treated with aspirin was observed in the concentration range of 1 10(-1)~10(-7)mol/L. The mean tumor volume and weight in nude mice treated with aspirin were significantly lower than those of the control group. The inhibiting rate for HCC xenografts was 71.62% in the aspirin group. After exposure to aspirin (31 10(-3)mol/L) for 48 hours, HCC cells presented some morphologic features of apoptosis. The apoptosis index was markedly higher in the aspirin group (8.90% 1.32%) than in the control group (0.50% 0.35%, P<0.01). A typical subdiploid peak before G0/G1 phase with an apoptosis rate as 12.79% was also observed. CONCLUSIONS: Aspirin inhibits the proliferation and increases the apoptosis of human HCC cells not only in vitro but also in vivo.