银杏内酯B调控JAK2/STAT3信号通路对食管癌细胞增殖及凋亡的影响OACSTPCD
Effects of Ginkgolide B on Proliferation and Apoptosis of Esophageal Cancer Cells by Regulating JAK2/STAT3 Signaling Pathway
为研究银杏内酯B对食管癌细胞增殖和凋亡的作用及相关机制,采用体外培养人食管癌OE19细胞,将其分为对照组(不做干预)、低/中/高剂量试验组(分别加入6.25、12.50、25.00 μmol/L银杏内酯B)、银杏内酯B组(12.50 μmol/L银杏内酯B)、阳性药物组(4 mg/L顺铂)、抑制剂组[12.50 μmol/L银杏内酯B+10.00 μmol/L Janus激酶2/转录激活因子3(JAK2/STAT3)通路抑制剂AG490]、激活剂组(12.50 μmol/L银杏内酯B+0.50 μmol/L JAK2/STAT3通路激活剂Colivelin),干预24 h后,采用细胞计数试剂盒-8(CCK-8)、5-乙炔基-2'脱氧尿嘧啶核苷(EdU)法、Hoechst 33258染色法、实时荧光定量PCR(RT-qPCR)和蛋白免疫印迹(WB)法检测细胞的活力、增殖率、凋亡率及相关因子的表达水平.结果显示,与对照组相比,中/高剂量试验组与阳性药物组的细胞活力降低(P<0.05),因此,本研究选择有显著差异且较低浓度的12.50 μmol/L银杏内酯B作为银杏内酯B组进行后续试验.与对照组相比,银杏内酯B组和阳性药物组细胞的增殖率、Cyclin D1的mRNA和蛋白质、p-JAK2、p-STAT3蛋白的表达水平降低,凋亡率、Caspase-3的mRNA和蛋白质的表达水平升高(P<0.05).与银杏内酯B组相比,抑制剂组各指标变化进一步增强(P<0.05),激活剂组则显著逆转了上述指标的变化(P<0.05).银杏内酯B能够通过下调JAK2/STAT3信号通路抑制OE19细胞的增殖,促进食管癌细胞凋亡.本研究揭示了银杏内酯B新抗癌机制,为食管癌的研究提供了理论依据.
To investigate the effects of ginkgolide B on the proliferation and apoptosis of esophageal cancer cells and the related mechanisms.Human esophageal cancer OE19 cells were cultured in vitro.They were divided into control group(no intervention),low/medium/high dose test group(adding 6.25,12.50 and 25.00 μmol/L ginkgolide B,respectively),ginkgolide B group(12.50 μmol/L ginkgolide B),positive drug group(4 mg/L cisplatin)and inhibitor group[12.50 μmol/L ginkgolide B+10.00 μmol/L ja-nus kinase 2/transcriptional activator 3(JAK2/STAT3)pathway inhibitor AG490]and activator group(12.50 μmol/L ginkgolide B+0.50 μmol/L JAK2/STAT3 pathway activator Colivelin),24 h after intervention,cell count kit 8(CCK-8),5-acetyl-2'deoxy-uridine(EdU)method,Hoechst 33258 staining,real-time fluorescence quantitative PCR(RT-qPCR)and protein immunoblot(WB)were used to detect cell viability,proliferation rate,apoptosis rate and expression levels of related factors.The results show that:compared with the control group,the cell viability of the medium/high dose test group and positive drug group was decreased(P<0.05),therefore,in this study,12.50 μmol/L ginkgolide B group with significant difference and lower concentration was se-lected as ginkgolide B group for follow-up tests.Compared with the control group,the cell proliferation rate,Cyclin D1 mRNA and protein expression levels,p-JAK2 and p-STAT3 protein expression levels of ginkgolide B group and positive drug group were decreased,while the apoptosis rate and Caspase-3 mRNA and protein expression levels were increased(P<0.05).Compared with the ginkgolide B group,the changes of all indexes in inhibitor group were further enhanced(P<0.05).while those in activator group were significantly reversed(P<0.05).Ginkgolide B can inhibit the proliferation of OE19 cells and promote apoptosis of esophageal cancer cells by down-regulating JAK2/STAT3 signaling pathway.This study revealed a new anticancer mechanism of ginkgolide B and provided a theoretical basis for the study of esophageal cancer.
殷星;侯永超;杨利姣;张萌
邯郸市第一医院肿瘤科,邯郸 056002
基础医学
食管癌银杏内酯BJanus激酶2/转录激活因子3增殖凋亡
esophageal cancerginkgolide Bjanus kinase 2/transcriptional activator 3proliferationapoptosis
《激光生物学报》 2024 (002)
185-192 / 8
河北省医学科学研究课题项目(20231909).
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