Lovastatin-induced apoptosis in human melanoma cell lines
Lovastatin-induced apoptosis in human melanoma cell lines
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DOI：
10.1097/00008390-200504000-00001
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发表时间：
2005-04-01
影响因子：
2.2
通讯作者：
Dellavalle, RP
中科院分区：
文献类型：
--
作者：
Shellman, YG;Ribble, D;Dellavalle, RP
降胆固醇药物他汀类药物抑制细胞增殖，并诱导包括黑色素瘤在内的一系列癌细胞株凋亡。我们在体外研究了洛伐他汀对人黑色素瘤细胞系的凋亡作用机制。用细胞滴度96(TM)水溶液细胞增殖试验(MTS法)检测他汀类药物对多种细胞株的细胞毒作用。采用溴化乙锭和吖啶橙形态分析、Annexin V细胞凋亡检测试剂盒和活性caspase 3检测细胞凋亡率。为了更好地确定介导洛伐他汀细胞毒性的分子机制，进行了法尼基焦磷酸和香叶基焦磷酸加成实验。洛伐他汀对人和小鼠黑色素瘤细胞有细胞毒性作用，但对表皮样癌细胞系A431无毒性作用。对于人黑色素瘤细胞，洛伐他汀使细胞变圆，溴化乙锭和吖啶橙染色及Annexin V凋亡检测试剂盒检测到的细胞凋亡率增加，caspase 3活性增加50倍，证实了洛伐他汀诱导了细胞凋亡。加入香叶基香叶基焦磷酸，而不是法尼基焦磷酸，逆转了洛伐他汀在A375细胞中的作用。在测试的五种他汀类药物中，普伐他汀对杀死黑色素瘤的效果最差
The cholesterol-lowering medications, statins, inhibit cellular proliferation and induce apoptosis in an array of cancer cell lines, including melanoma. We investigated the apoptotic mechanism of lovastatin on human melanoma cell lines in vitro. The cytotoxicity of statins on multiple cell lines was examined by Cell Titer 96 (TM) Aqueous One solution cell proliferation assay (MTS assay). Apoptosis was assayed by ethidium bromide and acridine orange morphologic assays, an Annexin V apoptosis detection kit and active caspase 3 assays. Farnesyl pyrophosphate and geranylgeranyl pyrophosphate add-back experiments were performed to better define the molecular mechanisms mediating lovastatin cytotoxicity. Lovastatin caused cytotoxicity in human and murine melanoma cells, but did not induce toxicity in an epidermoid carcinoma cell line A431. For human melanoma cells, lovastatin precipitated cell rounding, increased the percentage of apoptotic cells detected by ethidium bromide and acridine orange staining and by the Annexin V apoptosis detection kit, and resulted in a 50-fold increase in active caspase 3, corroborating that lovastatin induced apoptosis. Adding back geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate, reversed the effects of lovastatin in A375 cells. Of the five statins tested, pravastatin was least effective in killing melanoma