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目的研究过氧化物酶体增殖物激活受体γ(peroxisome proliferator activated receptor γ,PPARγ)激动剂ciglitazone对人肝癌细胞株 HepG2体内、外生长的影响,并探讨其可能机制。方法培养HepG2细胞,加入不同浓度的ciglitazone,用生长曲线检测HepG2细胞体外生长情况,用流式细胞仪进行细胞周期分析; Western blot检测ciglitazone对PPARγ蛋白表达的影响。建立裸鼠肝癌动物模型,随机将其分为两组:对照组(A组,10只),ciglita zone注射组(B组,10只),B组隔天注射ciglitazone 100μ(100 μmol/L)连续15次,对照组注射100 μL生理盐水,1个月后,切除瘤灶、称瘤重、计算抑瘤率。标本用Western blot检测细胞周期素D1(cyelinD1)、细胞周期素依赖性激酶抑制子P21蛋白的表达。结果(1)ciglitazone体外抑制HepG2细胞生长,并呈现明显时间和剂量依赖性。(2)经ciglitazone处理后PPARγ蛋白表达增加。(3) 经ciglitazone治疗后,A组、B组的瘤重分别为3．73±0．22g,2．60±0．35g,B组的抑瘤率达30％,A组的cyclinD1较B组明显增高,A 组的P21蛋白表达水平较B组明显降低。结论 Ciglitazone能抑制肝癌HepG2细胞的恶性增殖,其抑制作用呈明显的时间及剂量依赖性,并诱导其分化,其机制与PPARγ干预细胞周期的调控有关。
Objective To investigate the effects of ciglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) agonist, on the growth of HepG2 in vitro and in vivo, and to explore its possible mechanism. Methods HepG2 cells were cultured, and different concentrations of ciglitazone were added. Growth curves of HepG2 cells in vitro were detected by growth curve. Cell cycle analysis was performed by flow cytometry. The effect of ciglitazone on the expression of PPARγ protein was detected by Western blot. An animal model of hepatocellular carcinoma in nude mice was established and randomly divided into two groups: the control group (group A, 10), the ciglita zone injection group (group B, 10), and the group B injected ciglitazone 100 μ (100 μmol/L) every other day. For 15 consecutive times, the control group was injected with 100 μL normal saline. After 1 month, the tumor was resected, the tumor weight was weighed, and the tumor inhibition rate was calculated. Western blot was used to detect the expression of cyclin D1 (cyelinD1) and cyclin-dependent kinase inhibitor P21. Results (1) Ciglitazone inhibited the growth of HepG2 cells in vitro and showed significant time and dose dependence. (2) Increased PPARγ protein expression after ciglitazone treatment. (3) After treatment with ciglitazone, the tumor weights in group A and B were 3.73±0.22 g, 2.60±0.35 g, respectively. The inhibition rate in group B was 30%. The cyclin D1 in group A was higher than that in B group. The group was significantly higher, and the expression of P21 protein in group A was significantly lower than that in group B. Conclusion Ciglitazone can inhibit the malignant proliferation of hepatocellular carcinoma HepG2 cells. The inhibitory effect of Ciglitazone is time-and dose-dependent, and induces its differentiation. The mechanism is related to the regulation of PPARγ intervention cell cycle.