紫草素调控AMPK/mTOR信号通路对人食管癌细胞增殖、凋亡、迁移、侵袭和顺铂耐药的影响OA
Impact of shikonin on proliferation,apoptosis,migration,invasion,and cisplatin resistance of human esophageal cancer cells through AMPK/mTOR signaling pathway regulation
目的 探讨紫草素调控AMP活化蛋白激酶(AMPK)/雷帕霉素靶蛋白(mTOR)信号通路对人食管癌细胞增殖、凋亡、迁移、侵袭和顺铂耐药的影响.方法 将对数生长期的KYSE150细胞分为对照组、低-紫草素(0.5 mol/L)组、高-紫草素(2.0 mol/L)组、化合物C(10 μmol/L)组、高-紫草素+化合物C组,孵育24 h后,用MTT法检测细胞增殖率及耐药性;流式细胞术、Transwell实验检测细胞凋亡、迁移与侵袭;实时定量PCR检测自噬相关基因(P62、LC3)mRNA表达水平;Western blotting检测多药耐药相关蛋白1(MRP1)、端粒酶抑制因子(PINX1)、增殖细胞核抗原(PCNA)、Bcl-2相关X蛋白(Bax)、p-AMPK/AMPK、p-mTOR/mTOR表达.结果 与对照组相比,低-紫草素组、高-紫草素组490 nm处吸光度(OD490)、半数抑制浓度(IC50)、侵袭与迁移数、P62 mRNA表达、p-mTOR/mTOR、MRP1、PCNA表达降低,凋亡率、LC3 mRNA表达、p-AMPK/AMPK、PINX1、Bax表达增加(P<0.05);化合物C减弱了高-紫草素对KYSE150细胞恶性行为的抑制作用.结论 紫草素通过上调AMPK/mTOR信号通路抑制人食管癌细胞增殖、迁移、侵袭,促进其凋亡,提高顺铂敏感性.
Objective To investigate the impact of shikonin on proliferation,apoptosis,migration,invasion,and cisplatin resistance of human esophageal cancer cells through the regulation of the adenosine 5'-monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)signaling pathway.Methods KYSE150 cells in logarithmic growth phase were assigned to the control,low-shikonin(0.5 mol/L),high-shikonin(2.0 mol/L),compound C(10 μmol/L),and high-shikonin+compound C groups.After 24 h of incubation,the cell proliferation rate and drug resistance sensitivity were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphe-nyltetrazolium bromide(MTT)assay;cell apoptosis,migration,and invasion were examined using flow cytometry and the Transwell assay;and the expression levels of autophagy-related gene(P62 and LC3)mRNAs were determined using real-time quantitative PCR.The expression of multidrug resistance-related protein 1(MRP1),PIN2/TERF1-interacting telomerase inhibitor 1(PINX1),proliferating cell nuclear antigen(PCNA),Bcl-2 associated X protein(Bcl-2)associated X protein,phosphorylated(p)-AMPK/AMPK,and p-mTOR/mTOR was analyzed using Western blotting.Results Compared with the control group,the low-and high-shikonin groups showed decreased absorbance(OD490),half-maximal inhibitory concentration(IC50),invasion and migration numbers,P62 mRNA expression,p-mTOR/mTOR,MRP1,and PCNA expressions(P<0.05),whereas the apoptosis rate as well as LC3 mRNA,p-AMPK/AMPK,PINX1,and Bax expressions increased.Compound C weakened the inhibitory effect of high levels of shikonin on the malignant behavior of KYSE150 cells.Conclusion Shikonin inhibits the proliferation,migration,and invasion of human esophageal cancer cells,promotes apoptosis,and enhances cisplatin sensitivity by upregulating the AMPK/mTOR signaling pathway.
翟明慧;袁殿宝;吴文娟
河北北方学院附属第一医院 肿瘤内科,河北 张家口 075061河北北方学院附属第一医院 消化内镜科,河北 张家口 075061河北北方学院附属第一医院 肿瘤内科,河北 张家口 075061
医药卫生
紫草素AMPK/mTOR信号通路食管癌增殖迁移与侵袭顺铂凋亡
shikoninAMPK/mTOR signaling pathwayesophageal cancerproliferationmigration and invasioncisplatinapoptosis
《中国医科大学学报》 2026 (4)
295-300,6
河北省医学科学研究课题计划(20210617)
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