盐酸小檗碱通过P13K/AKT信号通路抑制MMP2和MMP9的表达影响膀胱癌T24细胞侵袭性

Berberine hydrochloride inhibits bladder cancer cell T24 invasion through inhibiting the expression of MMP2 and MMP9 via P13K/AKT signaling pathway

目的:探讨盐酸小檗碱(Berberine hydrochloride)对膀胱癌T24细胞侵袭能力的影响及机制.方法:采用利用CCK8法检测膀胱癌T24细胞的生存率;transwell侵袭试验检测盐酸小檗碱对T24细胞侵袭能力的影响;Western-blotting分析盐酸小檗碱对P13K/AKT通路相关因子(PI3K、p-PI3K、AKT、p-AKT),细胞基质金属蛋白酶(MMP2、MMP9)蛋白表达的改变.结果:CCK8显示盐酸小檗碱对T24细胞的增殖抑制呈浓度和时间依赖性(P<0.05);与对照组比较,经盐酸小檗碱处理后膀胱癌T24细胞侵袭能力明显降低.P13K抑制剂LY294002可通过抑制P13K/AKT通路活化,抑制MMP2和MMP9的表达,相对应的盐酸小檗碱处理后膀胱癌T24细胞p-PI3K、pAKT、MMP2、MMP9蛋白表达下降(P<0.05).结论:盐酸小檗碱可有效抑制膀胱癌T24细胞侵袭能力,其机制可能是通过调控P13K/AKT通路抑制MMP2和MMP9的表达.

Aim：To investigate whether Berberine hydrochloride can inhibit the invasion of bladder cancer cell line T24 and the underlying mechanisms.Methods：T24 cells were cultured with different concentrations of Berberine hydrochloride,and CCK8 assay was used to evaluate the cell inhibition rates. Cell invasion capabilities were evaluated by means of transwell matrix penetration assays.Activities and expressions of P13K/AKT signaling pathway-related factors （PI3K、p-PI3K、AKT、p-AKT）and invasion-related proteins matrix-metallopeptidase 2 （MMP-2）and MMP-9,were analyzed by Western blotting.Re-sults：Berberine hydrochloride caused concentration-and time-dependent inhibition of proliferation of T24 cells.T24 cells treated with Berberine hydrochloride showed significantly decreased invasion capabil-ities （P 〈0.05）.Western blotting demonstrated that P13K inhibitors （LY294002）can inhibit the ex-pression of MMP2 and MMP9.Moreover,expressions of p-PI3K,p-AKT,MMP2 and MMP9 were sup-pressed by Berberine hydrochloride in T24 cells （P 〈0.05 or P 〈0.01）.Conclusion：Berberine hydro-chloride may play a role to inhibit bladder cancer cell line T24 invasion through suppressing the expres-sions of MMP2 and MMP9 via P13K/AKT signaling pathway.