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目的考察汉防己碱(tetrandrine,Tet)对肝癌Hep3b和Hep3b/5-Fu细胞生长的影响。方法采用体外细胞培养,结合流式细胞术、MTT和Western blot方法研究Tet(0.33～1.0μg/ml)对肝癌Hep3b及Hep3b/5-Fu细胞生长的作用特点。结果 Tet在0.33～1.0μg/ml时呈浓度依赖性降低Hep3b细胞存活率;0.5和1.0μg/ml显著提高5-Fu对Hep3b细胞的IC50,但降低5-Fu对Hep3b/5-Fu细胞的IC50;0.33μg/ml的Tet明显增加cDDP对Hep3b/5-Fu细胞的IC50,而0.5和1.0μg/ml显著降低cDDP对Hep3b/5-Fu细胞的IC50(P<0.01)。1.0μg/ml的Tet作用48 h后使Hep3b细胞中的P-gp和MRP1表达明显上调(P<0.05)。Tet单用对Hep3b细胞生长有一定抑制作用,高浓度Tet逆转Hep3b/5-Fu细胞对5-Fu耐药和增强cDDP对Hep3b/5-Fu细胞生长的抑制作用,但低浓度分别促进Hep3b细胞和Hep3b/5-FU细胞对5-Fu和cDDP耐药。结论 Tet对Hep3b和Hep3b/5-Fu细胞生长呈浓度相关的双向作用,其促进耐药细胞发展的机制至少与提升P-gp和MRP1表达有关。
Objective To investigate the effect of tetrandrine (Tet) on the growth of Hep3b and Hep3b / 5-Fu cells. Methods The effects of Tet (0.33 ~ 1.0μg / ml) on the growth of Hep3b and Hep3b / 5-Fu cells were studied by in vitro cell culture combined with flow cytometry, MTT and Western blot. Results Tet at a concentration of 0.33 ~ 1.0μg / ml reduced the survival rate of Hep3b cells in a concentration-dependent manner; 0.5 and 1.0μg / ml significantly increased the IC50 of Hep3b cells by 5-Fu, but decreased the inhibitory effect of 5-Fu on Hep3b / 5-Fu cells IC50; 0.33 μg / ml Tet significantly increased the IC50 of cDDP on Hep3b / 5-Fu cells, while 0.5 and 1.0 μg / ml significantly reduced the IC50 of cDDP on Hep3b / 5-Fu cells (P <0.01). After treated with 1.0μg / ml Tet for 48 hours, the expression of P-gp and MRP1 in Hep3b cells were significantly up-regulated (P <0.05). Tet alone inhibited the growth of Hep3b cells. High concentrations of Tet reversed the drug resistance of Hep3b / 5-Fu cells to 5-Fu and increased the inhibitory effect of cDDP on Hep3b / 5-Fu cells. However, And Hep3b / 5-FU cells were resistant to 5-Fu and cDDP. Conclusions Tet has a concentration-dependent bidirectional effect on the growth of Hep3b and Hep3b / 5-Fu cells, and its mechanism of promoting the development of drug-resistant cells is at least related to enhancing the expression of P-gp and MRP1.