Astragaloside IV reverses MNNG‐induced precancerous lesions of gastric carcinoma in rats: Regulation on glycolysis through miRNA‐34a/LDHA pathway |
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Authors: | Chengzhe Zhang Tiantian Cai Xiaohui Zeng Dake Cai Yuxing Chen Xuejun Huang Haining Gan Juncheng Zhuo Ziming Zhao Huafeng Pan Siyi Li |
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Institution: | 1. Guangzhou University of Chinese Medicine, Guangzhou, China;2. Guangdong Province Engineering Technology Research Institute of T.C.M., Guangzhou, China;3. Guangdong Provincial key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou, Guangdong, China |
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Abstract: | 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. |
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Keywords: | Astragaloside IV Astragalus membranaceus glycolysis LDHA miRNA‐34a precancerous lesions of gastric carcinoma |
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