氨氯地平对小鼠肝癌H_(22)细胞的抑制作用及其机制

Inhibitory Effect of Amlodipine on Murine Hepatoma H_(22) Cells and Its Mechanism

目的探讨氨氯地平对小鼠肝癌H22细胞的抑制作用及其机制。方法采用MTT法检测氨氯地平对小鼠肝癌H22细胞增殖的影响。建立肝癌H22荷瘤小鼠模型,观察氨氯地平对荷瘤小鼠肿瘤的抑瘤率;HE染色观察肿瘤组织的病理改变;免疫组织化学方法检测肿瘤组织中bcl-2和bax蛋白的表达水平。结果氨氯地平作用48h可显著抑制小鼠肝癌H22细胞增殖,且呈剂量依赖性,其半数抑制浓度为5.6×10-3mg/ml。体内试验显示,氨氯地平(3和10mg/kg·d)灌胃给药10d能显著抑制H22荷瘤小鼠肿瘤生长;HE染色可见,氨氯地平给药组小鼠肿瘤细胞核染色变浅,细胞排列紧密;免疫组化显示,氨氯地平给药组小鼠肿瘤组织内bcl-2蛋白表达下调,而bax蛋白表达上调。结论氨氯地平具有明显的抑瘤作用,其抑瘤机制可能与诱导肿瘤细胞凋亡相关。

Objective To investigate the inhibitory effect of amlodipine on murine hepatoma H22cells and its potential mechanism. Methods The effect of amlodipine on the proliferation of H22 cells was determined by MTT method. H22 cells-bearing mouse model was established, based on which the inhibiting rate of amlodipine to tumor was observed. The pathological change of tumor tissue was observed by HE staining. The expression levels of bcl-2 and bax proteins in tumor tissue were determined by immunohistochemical method. Results The treatment with amlodipine for 48 h inhibited the proliferation of H22 cells significantly, and the inhibitory effect was dose-dependent. The median inhibiting concentration of amlodipine was 5. 6 × 10-3 mg / ml. In vivo test showed that intragastric administration with amlodipine at both dosages of 3 and 10 mg / kg·d for 10 d significantly inhibited the growths of tumors in H22 cells-bearing mice. HE staining showed that the nuclei of tumor cells of mice treated with amlodipine were stained lightly and arranged tightly. Immunohistochemical assay proved that the expression of bcl-2 protein in tumor tissues of mice treated with amlodipine was down-regulated, while that of bax protein was up-regulated. Conclusion Amlodipine showed significantly inhibitory effect on hepatoma, of which the mechanism might be associated with induction of tumor cell apoptosis.