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目的探讨环孢素A(CsA)与他克莫司(FK506)对肝癌的增殖、凋亡、复发及转移的影响。方法培养人肝癌细胞HepG-2,分别经5、10、100、500、1 000、5 000μg/L的CsA、FK506处理24~48 h后,采用噻唑蓝(MTT)法检测细胞增殖、流式细胞术测定细胞周期及细胞凋亡、荧光定量聚合酶链反应(PCR)检测转化生长因子(TGF)-β、细胞间黏附分子(ICAM)、骨桥蛋白(OPN)。结果肝癌细胞增殖能力48 h明显受到抑制.CsA、FK506使G_2期显著延长;FK506在小于100 μg/L及CSA在小于1 000μg/L时,随浓度增加,肝癌凋亡率逐渐增加,当两者分别超过100、1 000 μg/L时,则出现凋亡率减低;FK506、CSA分别在100、1 000μg/L低浓度时对OPN无影响,在 1 000、5 000μg/L高浓度时基因量显著增加。FK506在低浓度时对ICAM及TGF-β无影响,在高浓度时基因量显著增加;而CSA对两者无明显影响。结论 CsA、FKS06均对肝癌增殖有抑制作用,使G_2期阻滞,促凋亡;低浓度时对肝癌转移无影响,高浓度时增加转移危险。
Objective To investigate the effects of cyclosporin A (CsA) and tacrolimus (FK506) on the proliferation, apoptosis, recurrence and metastasis of hepatocellular carcinoma. Methods HepG-2 cells were cultured and treated with 5, 10, 100, 500, 1000 and 5000μg / L of CsA and FK506 for 24-48 h respectively. Cell proliferation was measured by MTT assay. Flow cytometry Cytometry and cell apoptosis were measured by cytometry. Transforming growth factor (TGF) -β, ICAM and osteopontin (OPN) were detected by fluorescence quantitative polymerase chain reaction (PCR). Results The proliferation of hepatocellular carcinoma cells 48 h was significantly inhibited. CsA and FK506 prolonged G_2 phase. When FK506 was less than 100 μg / L and CSA was less than 1 000 μg / L, the apoptotic rate of HCC increased with the increasing of FK506 concentration. , The apoptotic rate decreased. FK506 and CSA had no effect on OPN at the concentrations of 100 and 1 000 μg / L, respectively, and significantly increased at 1 000 and 5 000 μg / L. FK506 had no effect on ICAM and TGF-β at low concentration, but significantly increased at high concentration. However, CSA had no significant effect on both. Conclusion Both CsA and FKS06 can inhibit the proliferation of HCC and block and promote the apoptosis in G 2 phase. However, CsA and FKS06 have no effect on the metastasis of HCC at low concentration and increase the metastasis at high concentration.