Guangzhou University of Chinese Medicine, Guangzhou, Guanghdong, 510000, China; Department of Respiratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou,Guanghdong, 510000, China.
Guangzhou University of Chinese Medicine, Guangzhou, Guanghdong, 510000, China; Guangdong Province Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou, Guanghdong, 510000, China; Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou, Guanghdong, 510000, China.
Biomed Pharmacother. 2019 Dec;120:109427. doi: 10.1016/j.biopha.2019.109427. Epub 2019 Oct 21.
Gastric cancer is recognized as one of the most common cancer. In-depth research of gastric precancerous lesions (GPL) plays an important role in preventing the occurrence of gastric cancer. Meanwhile, traditional treatment provides a novel sight in the prevention of occurrence and development of gastric cancer. The current study was designed to assess the effects of therapy with Weipixiao (WPX) decoction on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced GPL rats and the underlying molecular mechanisms. After 10-weeks treatment, all rats were sacrificed. Histopathological changes of gastric tissue were assessed via hematoxylin-eosin (HE) and High-iron diamine-Alcian blue-Periodic acid-Schiff (HID-AB-PAS) staining. To be fully evidenced, RT-qPCR, Western blot and immunohistochemistry were used to detect the expressions of LDHA, CD147, HIF-1α, MCT4, PI3K, AKT, mTOR and miRNA-34a, which were crucial factors for evaluating GPL in the aspect of glycolysis pathogenesis. According to the results of HE and HID-AB-PAS staining, it could be confirmed that MNNG-induced GPL rats were obviously reversed by WPX decoction. Additionally, the increased gene levels of LDHA, CD147, MCT4, PI3K, AKT, mTOR and HIF-1α in model group were down-regulated by WPX decoction, while miRNA-34a expression was decreased and up-regulated by WPX decoction. The significantly increased protein levels of LDHA, CD147, MCT4, PI3K, AKT, mTOR and HIF-1α induced by MNNG were attenuated in rats treated with WPX decoction. In brief, the findings of this study imply that abnormal glycolysis in MNNG-induced GPL rats was relieved by WPX decoction via regulation of the expressions of LDHA, CD147, HIF-1α, MCT4, PI3K, AKT, mTOR and miRNA-34a.
胃癌被认为是最常见的癌症之一。深入研究胃癌前病变（GPL）对于预防胃癌的发生具有重要作用。同时，传统治疗为预防胃癌的发生和发展提供了新的视角。本研究旨在评估胃痞消（WPX）汤对 N-甲基-N'-硝基-N-亚硝基胍（MNNG）诱导的 GPL 大鼠的治疗效果及其潜在的分子机制。经过 10 周的治疗后，所有大鼠均被处死。通过苏木精-伊红（HE）和高铁二胺-阿利新蓝-过碘酸-雪夫（HID-AB-PAS）染色评估胃组织的组织病理学变化。为了充分证明，使用 RT-qPCR、Western blot 和免疫组织化学检测 LDHA、CD147、HIF-1α、MCT4、PI3K、AKT、mTOR 和 miRNA-34a 的表达，这些是评估 GPL 在糖酵解发病机制方面的关键因素。根据 HE 和 HID-AB-PAS 染色的结果，可以确认 WPX 汤明显逆转了 MNNG 诱导的 GPL 大鼠。此外，WPX 汤降低了模型组中 LDHA、CD147、MCT4、PI3K、AKT、mTOR 和 HIF-1α 的基因水平，而 miRNA-34a 的表达则被 WPX 汤下调和上调。MNNG 诱导的大鼠中 LDHA、CD147、MCT4、PI3K、AKT、mTOR 和 HIF-1α 的蛋白水平显著增加，WPX 汤治疗后减弱。总之，本研究的结果表明，WPX 汤通过调节 LDHA、CD147、HIF-1α、MCT4、PI3K、AKT、mTOR 和 miRNA-34a 的表达，缓解了 MNNG 诱导的 GPL 大鼠的异常糖酵解。
