6-姜辣素对黑色素瘤细胞增殖和凋亡的影响及机制研究  

Inhibitory effect of 6-gingerol on proliferation and apoptosis of melanoma cells via regulating endoplasmic reticulum stress

作　　者：李利萍 赖劲东 黄艳[2] 林新瑜 Li-ping Li;Jin-dong Lai;Yan Huang;Xin-yu Lin(Department of Dermatology,Affiliated Hospital of Southwest Medical University,Luzhou,Sichuan 646000,China;Department of Dermatology,Suining First People's Hospital,Suining,Sichuan 629000,China)

机构地区：[1]西南医科大学附属医院皮肤科,四川泸州646000 [2]遂宁市第一人民医院皮肤科,四川遂宁629000

出　　处：《中国现代医学杂志》2019年第5期17-22,共6页China Journal of Modern Medicine

摘　　要：目的探究6-姜辣素对黑色素瘤细胞增殖和凋亡的影响及其分子机制。方法使用不同浓度6-姜辣素处理黑色素瘤细胞,采用MTT法检测黑色素瘤增殖能力的变化;流式细胞仪检测6-姜辣素对黑色素瘤细胞凋亡的影响;应用Western blotting检测黑色素瘤细胞半胱天冬氨酸蛋白酶3(Caspase-3)/活化型半胱天冬氨酸蛋白酶3(Cleaved-Caspase-3)、多聚腺苷二磷酸核糖聚合酶(PARP)/活化型多聚腺苷二磷酸核糖聚合酶(Cleaved-PARP)、免疫球蛋白结合蛋白(BIP)、肌醇激酶1(IRE1)和c-Jun氨基末端激酶(JNK)蛋白表达水平变化;敲减IRE1阻断内质网应激信号通路,检测6-姜辣素对黑色素瘤细胞增殖和凋亡的影响。结果6-姜辣素抑制黑色素瘤细胞增殖呈浓度依赖性,对M14和A375细胞的半数抑制浓度(IC50)分别为46.070和33.152μmol/L;6-姜辣素处理后,黑色素瘤细胞Cleaved-Caspase-3和Cleaved-PARP蛋白表达上调(P <0.05),细胞凋亡率升高(P <0.05);6-姜辣素激活内质网应激,BIP、IRE1和JNK蛋白表达上调(P <0.05);6-姜辣素处理IRE1基因敲减细胞,与对照组相比对细胞增殖抑制减弱、凋亡蛋白Cleaved-Caspase-3表达下调(P <0.05)。结论 6-姜辣素可通过激活内质网应激,抑制黑色素瘤细胞增殖并促进其凋亡,从而发挥抗肿瘤功能。Objective To explore the inhibitory effect of 6-gingerol on the proliferation and apoptosis of melanoma cells and its molecular mechanism.Methods Melanoma cells were treated with different concentrations of 6-gingerol.Cellular proliferation and apoptosis rate were identified by MTT and flow cytometry,respectively.The protein levels of Caspase-3/Cleaved-Caspase-3,PARP/Cleaved-PARP,BiP,IRE1 and JNK in melanoma cell line were measured by Western blotting.Endoplasmic reticulum stress signaling pathway was blocked by knockdown of IRE1 for further mechanism study.Result The 6-gingerol inhibited the proliferation of melanoma cells in a concentrationand time-dependent manner while apoptosis rate was enhanced(P<0.05).IC50 of 6-gingerol was 46.070 μmol and 33.152 μmol/L for M14 and A375 cell line,respectively.Treatment with 6-gingerol induced increased expression of Cleaved-Caspase-3 and cleaved-PARP(P<0.05).Endoplasmic reticulum stress was activated by 6-gingerol with increase of BiP,IRE1 and JNK.IRE1 knockdown reversed 6-gingerol-induced upregulation of proliferation,cleaved-Caspase-3(P<0.05).Conclusion The 6-gingerol inhibits proliferation of melanoma cell by activating the endoplasmic reticulum stress.

关 键 词：黑色素瘤 6-姜辣素 内质网应激 增殖 凋亡 

分 类 号：R739.5[医药卫生—肿瘤]