Astragaloside IV reverses MNNG-induced precancerous lesions of gastric carcinoma in rats: Regulation on glycolysis through miRNA-34a/LDHA pathway
Astragaloside IV reverses MNNG-induced precancerous lesions of gastric carcinoma in rats: Regulation on glycolysis through miRNA-34a/LDHA pathway
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黄芪甲苷 IV 逆转 MNNG 诱导的大鼠胃癌癌前病变：通过 miRNA-34a/LDHA 通路调节糖酵解
DOI：
10.1002/ptr.6070
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发表时间：
2018
影响因子：
7.2
通讯作者：
Pan H
中科院分区：
文献类型：
--
作者：
Zhang Chengzhe;Cai Tiantian;Zhuo Juncheng;Pan Huafeng;Li Siyi;Zhang Chengzhe;Zeng Xiaohui;Cai Dake;Chen Yuxing;Huang Xuejun;Gan Haining;Zhuo Juncheng;Zhao Ziming;Zhang Chengzhe;Zeng Xiaohui;Cai Dake;Chen Yuxing;Huang Xuejun;Gan Haining;Zhuo Juncheng;Pan H
本研究旨在探讨黄芪甲苷（ASIV）逆转N-甲基-N′-硝基-N-亚硝基胍（MNNG）诱导的胃癌前病变（PLGC）的机制。给药10周后处死所有大鼠。对胃组织进行组织病理学和电镜观察。为了充分证明，通过Western印迹和真实的实时定量聚合酶链反应（RT-qPCR）检测LDHA、p53、TIGAR、MCT 1、MCT 4、HIF-1α、CD 147和miRNA-34 a。如组织病理学和电子显微镜所示，可以清楚地观察到ASIV组的异型增生面积减少，表明MNNG诱导的PLGC被ASIV显著逆转。与模型组相比，ASIV组大鼠肝组织中LDHA、MCT 1、MCT 4、HIF-1α、CD 147、TIGAR基因表达明显降低，而miRNA-34 a表达明显升高。在ASIV处理的大鼠中，MNNG诱导的LDHA、MCT 1、MCT 4、HIF-1α和CD 147蛋白水平的显著上调减弱。相反，ASIV恢复了TIGAR的表达下降。有趣的是，在ASIV组中，MNNG诱导的p53表达上调进一步增加。总之，这些结果表明ASIV通过调节LDHA、p53、TIGAR、MCT 1、MCT 4、HIF-1α、CD 147和miRNA-34 a的表达来缓解异常糖酵解。
This study was designed to investigate the precancerous lesions of gastric carcinoma (PLGC)‐reversing mechanisms of astragaloside IV (ASIV) in N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG)‐induced PLGC rats. All rats were sacrificed after 10‐week treatment. Gastric tissue was analyzed by using histopathology and electron microscope. To be fully evidenced, LDHA, p53, TIGAR, MCT1, MCT4, HIF‐1α, CD147, and miRNA‐34a were detected by Western blotting and Real‐time Quantitative polymerase chain reaction (RT‐qPCR). As histopathology and electron microscope showed, it can be clearly observed that the area of dysplasia was reduced in ASIV groups, indicating that MNNG‐induced PLGC was markedly reversed by ASIV. Moreover, compared with model group, a significant decrease in gene expressions of LDHA, MCT1, MCT4, HIF‐1α, CD147, and TIGAR was observed whereas miRNA‐34a level was increased in ASIV groups. A significant up‐regulation induced by MNNG in protein levels of LDHA, MCT1, MCT4, HIF‐1α, and CD147 was attenuated in rats treated with ASIV. In contrast, the decreased expression of TIGAR was restored by ASIV. Interestingly, up‐regulation of p53 expression induced by MNNG was further increased in ASIV groups. In brief, these results implied that abnormal glycolysis was relieved by ASIV via regulation of the expressions of LDHA, p53, TIGAR, MCT1, MCT4, HIF‐1α, CD147, and miRNA‐34a.