Matrine inhibits invasiveness and metastasis of human malignant melanoma cell line A375 in vitro
Matrine inhibits invasiveness and metastasis of human malignant melanoma cell line A375 in vitro
复制标题
苦参碱体外抑制人恶性黑色素瘤细胞系A375的侵袭和转移
DOI：
10.1111/j.1365-4632.2008.03627.x
复制
发表时间：
2008-05-01
影响因子：
3.6
通讯作者：
Chen, Hong-chao
中科院分区：
文献类型：
--
作者：
Liu, Xiao-yan;Fang, Hong;Chen, Hong-chao
苦参碱是一种对恶性肿瘤具有显著抑制作用的中药。其对恶性肿瘤侵袭和转移的影响很少被报道。目的探讨苦参碱是否能体外抑制人恶性黑色素瘤A375细胞系的转移相关活性。方法采用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑（MTT）法和annexin - v -异硫氰酸荧光素/碘化丙啶（Annexin-V-FITC/PI）亲和法检测苦参碱对A375细胞增殖和诱导凋亡的影响。光镜、电镜观察A375细胞形态学变化。采用半定量逆转录聚合酶链反应（RT-PCR）和Western blotting检测肝素酶mRNA和蛋白的表达。采用细胞-基质粘附法和基质侵袭法检测苦参碱对A375细胞的粘附能力和侵袭性的影响。结果苦参碱对A375细胞的增殖有明显的抑制作用，且呈剂量依赖性和时间依赖性。它还以剂量依赖的方式诱导细胞凋亡。与对照组相比，不同浓度苦参碱处理后A375细胞的肝素酶mRNA和蛋白表达水平均显著降低，其粘附能力和侵袭性均显著降低。结论苦参碱具有抑制A375细胞侵袭和转移的作用。其机制可能与抑制细胞增殖、诱导细胞凋亡、下调肝素酶mRNA和蛋白表达有关。
Background Matrine is a traditional Chinese medicine with significant inhibitory activity against malignant tumors. Its effects on the invasiveness and metastasis of malignant tumors have rarely been reported.Aim To investigate whether matrine can inhibit the metastasis-related activities of the human malignant melanoma cell line A375 in vitro.Methods 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and Annexin-V-fluorescein isothiocyanate/propidium iodide (Annexin-V-FITC/PI) affinity assay were used to examine the effects of matrine on the proliferation and apoptosis induction of A375 cells. The morphologic changes of A375 cells were observed by light and electron microscopy. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were performed to evaluate the expression of heparanase mRNA and protein. The effect of matrine on the adhesion ability and invasiveness of treated A375 cells was tested by cell-Matrigel adhesion assay and Matrigel invasion assay, respectively.Results Matrine showed significant inhibition of the proliferation of A375 cells in a dose- and time-dependent manner. It also induced apoptosis in a dose-dependent manner. Compared with the control group, the levels of heparanase mRNA and protein expression of A375 cells treated with different concentrations of matrine were decreased significantly, as were their adhesion ability and invasiveness.Conclusions These findings indicate that matrine inhibits the invasiveness and metastasis of A375 cells in vitro. The mechanisms may be linked to the inhibition of cellular proliferation, induction of apoptosis, and downregulation of heparanase mRNA and protein expression.