摘要
目的研究萝卜硫素(sulforaphane,SFN)对A375黑色素瘤增殖、生长、凋亡和血管生成的影响及其作用机制。方法细胞增殖实验研究SFN对A375细胞增殖的影响;裸小鼠皮下移植瘤模型研究SFN对黑色素瘤体内生长的影响;流式细胞仪检测萝卜硫素对A375黑色素瘤细胞凋亡的影响;小管形成实验检测SFN对A375人黑色素瘤血管生成的影响;蛋白质印迹法检测SFN对A375细胞中调控增殖、凋亡及血管生成相关蛋白表达的影响,如Bax、Bcl-2、VEGF、b FGF、cleaved PARP、p-P38、t-P38、p-Erk、t-Erk。结果 SFN对A375细胞的增殖具有明显的抑制作用;SFN能够明显抑制A375裸鼠皮下移植瘤的体内生长;SFN能显著抑制肿瘤细胞诱导的血管生成;SFN对A375黑色素瘤细胞的凋亡无明显影响。机制研究发现,SFN对VEGF、b FGF、p-P38及p-Erk的表达具有抑制作用,但对Bcl-2、Bax及cleaved PARP蛋白的表达没有明显影响。结论萝卜硫素具有抗黑色素瘤体内生长的能力,其作用机制与调控黑色素瘤细胞的凋亡无关,而可能是通过抑制黑色素瘤的血管生成。
Objective To study the effect of SFN on tumor proliferation, growth, apoptosis and angiogenesis of A375 melanoma and its potential molecular mechanisms. Methods MTT was used to test the effect of SFN on proliferation of A375 melanoma. A375 melanoma xenograft model was used to detect the effect of SFN on tumor growth. Flow cytometry was used to examine the effect of SFN on apoptosis of A375 melanoma. The effect of SFN on tumor angiogenesis was determined by tube formation. The protein expression of VEGF, bFGF, Bcl-2, Bax, cleaved PARP, p-P38, t-P38, p-Erk, t-Erk were measured by western blot to explore the potential molecular mechanisms of SFN on regulation of tumor proliferation and angiogenesis. Results Compared to the control group, the proliferation of A375 melanoma was significant inhibited by SFN in vitro. Study on A375 melanoma xenograft model showed that SFN inhibited the growth of A375 melanoma in vivo significantly compared to the control group. SFN inhibited tumor cell-induced tube formation. To our surprise, treatment with SFN had no obvious effect on apoptosis of A375 melanoma. Mechanistic study found that the expression of VEGF,bFGF,p-P38 and p-Erk were significant inhibited by administration with SFN. However, SFN had no apparent effect on expression of apoptosis-related factors such as Bcl-2, Bax, and cleaved PARP. Conclusions SFN has anti-proliferation and anti-growth effects on A375 melanoma, and the potential mechanisms was not due to inhibition of apoptosis, but may associated with inhibition of tumor angiogenesis of A375 melanoma.
出处
《沈阳药科大学学报》
CSCD
北大核心
2017年第8期680-685,693,共7页
Journal of Shenyang Pharmaceutical University
关键词
萝卜硫素
黑色素瘤
生长
凋亡
血管生成
分子机制
sulforaphane
melanoma
sgrowth
apoptosis
tumor angiogenesis
molecular mechanism
