目的： 探讨木鳖子醇提物（ethanol extract of cochinchina momordica seed, CMSEE）诱导黑素瘤B16细胞分化的作用机制。 方法： CMSEE处理B16细胞后，瑞氏染色法观察B16细胞的形态变化；比色法检测B16细胞的黑素含量。Western blotting检测经CMSEE和p38、ERK通路抑制剂SB203580、SD98059分别处理后B16细胞中p-p38、p-ERK表达的变化。 结果： CMSEE可诱导B16细胞分化，使细胞的黑素量含量明显升高（P<0.01），10、20、40 μg/ml CMSEE处理组B16细胞的黑素量D值分别为（0.057±0.007）、（0.173±0.005）和（0.249±0.002），而对照组为（0.037±0.002）。20 μg/ml CMSEE处理B16细胞后，p-p38蛋白表达水平明显升高，处理60 min时的相对表达量最高，为对照组的5.6倍；而p-ERK表达水平明显降低（P<0.01），处理60 min时的相对表达量为对照组的25%倍。p38通路抑制剂SB203580可阻断CMSEE对B16细胞的分化诱导作用，而ERK通路抑制剂SD98059可增强CMSEE对B16细胞的分化诱导作用。 结论： p38通路和ERK通路的活化参与了CMSEE对B16细胞的分化诱导作用。

Objective：To study the mechanism of the differentiation of mouse melanoma B16 cells induced by ethanol extract of cochinchina momordica seed (CMSEE). Methods: After treated with CMSEE, morphological changes of B16 cells were observed by Giemsa staining, and melanin level was assessed by colorimetric method. Western blotting was used to measure the expression changes of phosphorylation p38 (p-p38) and ERK (p-ERK) in B16 cells after treatment with CMSEE and p38, ERK pathway inhibitors, SB203580 and SD98059. Results: CMSEE could induce the differentiation of B16 cells. The melanin level in B16 cells was significantly increased after CMSEE treatment (P<0.01), with D value being (0.057±0.007), (0.173±0.005) and (0.249±0.002) for 10, 20 and 40 μg/ml CMSEE and (0.037±0002) for control group. 20 μg/ml CMSEE elevated the level of p-p38 protein and blocked the expression of p-ERK (P<0.01) in B16 cells, and the expression level of p-p38 protein was 5.6 fold and p-ERK was 0.25 fold that of the control group after treatment with CMSEE for 60 min. SB203580, the inhibitor of p38 pathway, blocked CMSEE-induced B16 cell differentiation, and PD98059, the inhibitor of ERK pathway, elevated CMSEE-induced B16 cell differentiation. Conclusion: p38 and ERK signal pathway activations are involved in the differentiation of B16 melanoma cells induced by CMSEE.

河北省中医药管理局资助项目（No. 2011011）