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An SGLT2 inhibitor modulates SHH expression by activating AMPK to inhibit the migration and induce the apoptosis of cervical carcinoma cells.
Cancer Letters ( IF 9.1 ) Pub Date : 2020-09-12 , DOI: 10.1016/j.canlet.2020.09.005
Zipeng Xie 1 , Fang Wang 2 , Lingqiang Lin 1 , Shaoxian Duan 1 , Xiangyang Liu 3 , Xiaoyu Li 3 , Ting Li 3 , Mei Xue 3 , Ying Cheng 3 , He Ren 4 , Yi Zhu 1
Affiliation  

In addition to their hypoglycemic effect, sodium-glucose cotransporter 2 (SGLT2) inhibitors have many other benefits. In the present study, we examine the anticancer effect of the SGLT2 inhibitor empagliflozin using cervical carcinoma models. In vivo antitumor activities of empagliflozin were observed in a nude mouse model. Empagliflozin intervention and downregulation of Sonic Hedgehog Signaling Molecule (Shh) inhibited the migration and promoted the apoptosis of cervical cancer cells in nude mice. Compared with the control group, the empagliflozin treatment group had an increased level of AMP-activated protein kinase (AMPK) and decreased levels of Forkhead Box A1 (FOXA1) and SHH in tumor tissue. In vitro experiments also showed that empagliflozin (50 μM) inhibited the migration of cervical cancer cells and induced their apoptosis by activating the AMPK/FOXA1 pathway and inhibiting the expression of SHH. Kaplan-Meier survival analysis was used to determine the relationship between SHH expression and total survival time. The results showed that in cervical cancer patients, high SHH expression resulted in unfavorable overall survival. The downregulation of SHH with small interfering RNA (siRNA) inhibited the migration and invasion and promoted the apoptosis of HeLa cells. These findings show that empagliflozin has a potential therapeutic effect on cervical cancer. This effect was related to the activation of the AMPK pathway and the inhibition of SHH expression.



中文翻译:

SGLT2抑制剂通过激活AMPK来抑制子宫颈癌细胞的迁移并诱导其凋亡来调节SHH表达。

除了降血糖作用外,钠葡萄糖共转运蛋白2(SGLT2)抑制剂还有许多其他好处。在本研究中,我们使用宫颈癌模型检查了SGLT2抑制剂依帕格列净的抗癌作用。在裸鼠模型中观察到了依帕格列净的体内抗肿瘤活性。Empagliflozin干预和Sonic Hedgehog信号分子(Shh)的下调抑制了裸鼠的迁移并促进了子宫颈癌细胞的凋亡。与对照组相比,Empagliflozin治疗组在肿瘤组织中的AMP活化蛋白激酶(AMPK)水平升高,而Forkhead Box A1(FOXA1)和SHH水平降低。体外实验还显示,依帕格列净(50μM)通过激活AMPK / FOXA1途径和抑制SHH的表达来抑制子宫颈癌细胞的迁移并诱导其凋亡。Kaplan-Meier生存分析用于确定SHH表达与总生存时间之间的关系。结果表明,在宫颈癌患者中,SHH高表达导致总体生存不良。小干扰RNA(siRNA)对SHH的下调抑制了HeLa细胞的迁移和侵袭并促进了其凋亡。这些发现表明,依帕格列净对宫颈癌具有潜在的治疗作用。该作用与AMPK途径的激活和SHH表达的抑制有关。Kaplan-Meier生存分析用于确定SHH表达与总生存时间之间的关系。结果表明,在宫颈癌患者中,SHH高表达导致总体生存不良。小干扰RNA(siRNA)对SHH的下调抑制了HeLa细胞的迁移和侵袭并促进了其凋亡。这些发现表明,依帕格列净对宫颈癌具有潜在的治疗作用。该作用与AMPK途径的激活和SHH表达的抑制有关。Kaplan-Meier生存分析用于确定SHH表达与总生存时间之间的关系。结果表明,在宫颈癌患者中,SHH高表达导致总体生存不良。小干扰RNA(siRNA)对SHH的下调抑制了HeLa细胞的迁移和侵袭并促进了其凋亡。这些发现表明,依帕格列净对宫颈癌具有潜在的治疗作用。该作用与AMPK途径的激活和SHH表达的抑制有关。小干扰RNA(siRNA)对SHH的下调抑制了HeLa细胞的迁移和侵袭并促进了其凋亡。这些发现表明,依帕格列净对宫颈癌具有潜在的治疗作用。该作用与AMPK途径的激活和SHH表达的抑制有关。小干扰RNA(siRNA)对SHH的下调抑制了HeLa细胞的迁移和侵袭并促进了其凋亡。这些发现表明,依帕格列净对宫颈癌具有潜在的治疗作用。该作用与AMPK途径的激活和SHH表达的抑制有关。

更新日期:2020-09-13
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