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目的探讨HMG-CoA还原酶抑制剂(Statins)在体内外抑制肝细胞癌增殖和侵犯的作用及其机制。方法以不同浓度的普伐他汀(Pr)作用于培养的HepG2细胞,用噻唑蓝比色试验检测细胞的增殖活性,并观察细胞的形态学变化。建立HepG2细胞裸小鼠皮下移植瘤模型,腹腔注射浓度为5 g／L的Pr,每只每日10 ml／kg体重。观察肿瘤的生长情况,实验结束时切取肿瘤称重,检测血中AFP水平。肿瘤标本石蜡切片,免疫组织化学检测CyclinD1和FⅧRA的表达。结果 Pr作用96 h后明显抑制了HepG2细胞的生长,细胞出现明显的形态学改变。Pr也抑制裸小鼠皮下移植型肝癌的生长,Pr组和对照组瘤重分别是(0．246±0．129)g和(0．376±0．102)g(P< 0．05),抑瘤率34．6％。两组的AFP表达差异有统计学意义[(2．657±1．465)μg／L比(4．206± 1．204)μg／L,P<0．05]。Cydin D1在肿瘤间质的成纤维细胞表达,Pr组的积分吸光度(OPTID)为 219．40±24．00,对照组为451．54±47．97(P<0．05)。两组的微血管密度(MVD)分别为27．43± 6．83和41．22±6．26(P<0．05)。结论 Pr能抑制肝癌细胞的增殖,其机制主要是抑制肿瘤的血管形成和肿瘤基质中的成纤维细胞的增生。
Objective To investigate the effect and mechanism of HMG-CoA reductase inhibitor (Statins) on inhibiting the proliferation and invasion of hepatocellular carcinoma in vitro and in vivo. Methods HepG2 cells were cultured with different concentrations of pravastatin (Pr). Cell proliferation was measured by thiazolyl blue colorimetric assay. Morphological changes of cells were observed. A subcutaneous xenograft model of HepG2 cells in nude mice was established. Pr was injected intraperitoneally at a concentration of 5 g / L, and each was given a daily dose of 10 ml / kg of body weight. The growth of the tumor was observed. At the end of the experiment, the tumor was weighed and the level of AFP in the blood was measured. The paraffin sections of the tumor specimens were examined for the expression of CyclinD1 and FⅧRA by immunohistochemistry. Results After treated with Pr for 96 h, the growth of HepG2 cells was obviously inhibited, and obvious morphological changes of cells were observed. Pr also inhibited the growth of subcutaneous transplanted hepatocarcinoma in nude mice. The tumor weights in Pr group and control group were (0.246 ± 0.129) g and (0.376 ± 0.102) g, respectively (P <0.05) , Inhibition rate of 34.6%. The difference of AFP expression between the two groups was statistically significant [(2.657 ± 1.465) μg / L vs (4.206 ± 1.204) μg / L, P <0.05]. Cydin D1 was expressed in tumor stroma fibroblasts. The integral absorbance (OPTID) of Pr group was 219.40 ± 24.00 and that of control group was 451.54 ± 47.97 (P <0.05). The microvessel density (MVD) was 27.43 ± 6.83 and 41.22 ± 6.26 in both groups (P <0.05). Conclusion Pr can inhibit the proliferation of hepatocellular carcinoma cells. Its mechanism is mainly to inhibit tumor angiogenesis and proliferation of fibroblasts in tumor matrix.