黄芩苷增强阿霉素抗人舌癌细胞活性及其机制研究  

Effect of Baicalin on Activity and Mechanism of Doxorubicin against Human Tongue Cancer

作　　者：褚冬青 马春宇 CHU Dongqing;MA Chunyu(Jinzhou Medical University,Jinzhou 121000 Liaoning,China)

机构地区：[1]锦州医科大学,辽宁锦州121000

出　　处：《中药新药与临床药理》2019年第9期1062-1068,共7页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：辽宁省自然科学基金项目（20170540368）

摘　　要：目的探讨黄芩苷与阿霉素联合对人舌癌TCA-8113细胞凋亡、迁移的影响及其作用机制。方法采用MTT法检测黄芩苷、阿霉素、黄芩苷联合阿霉素对人舌癌TCA-8113细胞增殖的影响;采用Hoechst 33342染色法以及流式细胞术检测TCA-8113细胞凋亡情况;细胞划痕试验检测细胞迁移情况;Western Blot法检测TCA-8113细胞Bcl-2、Bax、Cleaved Caspase-3、p-FAK、FAK、p-Src、Src蛋白表达情况。结果黄芩苷呈剂量依赖性抑制人舌癌TCA-8113细胞的增殖,但浓度不超过40 mg·L-1的黄芩苷对TCA-8113细胞生长无明显影响。与单用阿霉素组(2.0 mg·L-1)比较,黄芩苷(40 mg·L-1)联合运用能明显提高阿霉素对人舌癌细胞增殖抑制作用,增敏倍数平均提高1.38倍(P<0.05);TCA-8113细胞凋亡率明显升高(P<0.01);抑制TCA-8113细胞的迁移能力明显增强(P<0.01);抗凋亡蛋白Bcl-2表达降低(P<0.01),促凋亡蛋白Bax、Cleaved Caspase-3的表达进一步增加(P<0.05);p-FAK、p-Src蛋白表达进一步受到明显抑制(P<0.05,P<0.01)。结论阿霉素和黄芩苷联合应用可增强诱导人舌癌TCA-8113细胞发生凋亡、抑制迁移,其协同增效机制可能与下调Bcl-2、p-FAK及p-Src蛋白表达有关。Objective To evaluate the effects of doxorubicin and baicalin on apoptosis and migration of human tongue cancer TCA-8113 cells,and to explore the mechanism of synergistic anti-tumor effect.Methods Methylazolium blue staining(MTT)was used to detect the effects of baicalin,doxorubicin,baicalin combined with doxorubicin,respectively,on the proliferation of human tongue cancer TCA-8113 cells.Hoechst 33342 and flow cytometry were used to detect apoptosis of TCA-8113 cells before and after application of the drugs.Wound healing method was used to detect the migration of TCA-8113 cells.Western Blot was used to detect expression of Bcl-2,Bax,Cleaved Caspase-3,p-FAK,FAK,p-Src,Src in TCA-8113 cells.Results Baicalin inhibited the proliferation of human tongue cancer TCA-8113 cells in a dose-dependent manner.Baicalin with a concentration of not more than 40 mg·L-1 had no effect on the growth of the above cells.Baicalin could significantly increase the proliferation inhibition effect of doxorubicin on human tongue cancer cells.The sensitization factor was increased by1.38 times on average,which was statistically significant compared with the doxorubicin group(P<0.05).The apoptosis of TCA-8113 cells increased significantly(P<0.01);migration of cells were inhibited(P<0.01).Baicalin sensitized the inhibition effect of anti-apoptosis by doxorubicin on human tongue cancer TCA-8113 cells.The expression of protein Bcl-2 was suppressed(P<0.01),and the expression of proapoptotic protein Bax and Cleaved Caspase-3 was further induced(P<0.05),the phosphorylation of FAK and Src proteins were inhibited(P<0.05,P<0.01).Conclusion The combination of doxorubicin and baicalin can significantly induce apoptosis and inhibit migration of human tongue cancer TCA-8113 cells.The synergistic anti-tumor mechanism may be related to down-regulating the expression of Bcl-2 and p-FAK,p-Src.

关 键 词：阿霉素 黄芩苷 协同作用 增敏 TCA-8113细胞 凋亡 迁移 

分 类 号：R285[医药卫生—中药学]