Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Guangdong Province Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou, Guangdong 510095, China; Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou, Guangdong, 510095, China.
Biomed Pharmacother. 2018 Aug;104:291-299. doi: 10.1016/j.biopha.2018.04.013. Epub 2018 May 25.
Gastric Cancer is one of the most common types of cancer. And the occurrence of gastric carcinoma is an evolutionary histopathological stage. As a result, further research of GPL, which is a borderline of gastric cancer, is indispensable for preventing the formation and development of gastric carcinoma. Several studies have demonstrated a correlation between the expression of autophagy, apoptosis and Gastric cancer (GC). However, the effects of autophagy and apoptosis on human gastric cancer progression, particularly on gastric precancerous lesions (GPL), have not totally been investigated. At present, Astragaloside IV(AS-IV) is a saponin purified from Astragalus membranaceous Bge, a traditional Chinese herb that has been widely used for more than 2000 y in the treatment of cancer, cardiovascular and immune disorders. This study was designed to investigate the mechanism of AS-IV protecting gastric mucosa in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced GPL rats. The lesions of GIM and GED were significantly ameliorated compared with the model rats, especially crowded tubular glandular and back-to-back tubular structure, which were the dangerous borderline between GPL and GC. Western Blot analysis showed that the ratio of Bcl-2/Bax and the protein expression of Bcl-XL, p53, Beclin1, p62, ATG5 and ATG12 were decreased and the level of Caspase3 was increased in the group of AS-IV compared with the model group; RT-PCR analysis showed that the gene expression Ambra1, Beclin1, ATG5, LC3 and p62 were decreased in the group of AS-IV compared with the model group. This research manifested that the occurrence of gastric cancer was preceded by a prolonged precancerous stage, which could be ameliorated by the AS-IV. Meanwhile, the mild and moderate stage of precancerous lesions is similar with gastric adenocarcinoma in critical biological processes, including inflammation, cell proliferation, differentiation. But this lesion is very different from cancer, because it does not appear obvious invasion and malignant lesions in this pathologic stag. Further, AS-IV could regulate p53 expression to activate the Ambra1/Beclin1 complex in GPL, and it will protect the gastric mucosal injury, prevent and cure gastric mucosal atrophy, intestinal metaplasia and atypical hyperplastic lesions. It provided a potential therapeutic strategy in reversing intestinal metaplasia and dysplasia of gastric precancerous lesions and protecting the gastric mucosa in GPL rats.
胃癌是最常见的癌症类型之一。而胃癌的发生是一个进化的组织病理学阶段。因此,进一步研究胃交界瘤(GPL),对于预防胃癌的形成和发展是必不可少的。几项研究表明,自噬、凋亡与胃癌(GC)之间存在相关性。然而,自噬和凋亡对人类胃癌进展的影响,特别是对胃癌前病变(GPL)的影响,尚未完全研究清楚。目前,黄芪甲苷(AS-IV)是从黄芪中提取的一种皂苷,黄芪是一种中药,在中国已经被广泛用于治疗癌症、心血管疾病和免疫紊乱超过 2000 年。本研究旨在探讨 AS-IV 对 N-甲基-N'-硝基-N-亚硝基胍(MNNG)诱导的 GPL 大鼠胃黏膜的保护机制。与模型大鼠相比,GIM 和 GED 病变明显改善,尤其是拥挤的管状腺和背靠背管状结构,这是 GPL 与 GC 之间的危险交界。Western Blot 分析显示,与模型组相比,AS-IV 组的 Bcl-2/Bax 比值以及 Bcl-XL、p53、Beclin1、p62、ATG5 和 ATG12 的蛋白表达降低,Caspase3 水平升高;RT-PCR 分析显示,与模型组相比,AS-IV 组的 Ambra1、Beclin1、ATG5、LC3 和 p62 基因表达降低。本研究表明,胃癌的发生是在一个漫长的癌前阶段之前发生的,AS-IV 可以改善这种情况。同时,癌前病变的轻度和中度阶段与临界生物学过程中的胃腺癌相似,包括炎症、细胞增殖、分化。但这种病变与癌症有很大的不同,因为在这个病理阶段并没有明显的侵袭和恶性病变。此外,AS-IV 可以调节 p53 表达,激活 GPL 中的 Ambra1/Beclin1 复合物,从而保护胃黏膜损伤,预防和治疗胃黏膜萎缩、肠上皮化生和不典型增生病变。为逆转 GPL 大鼠的肠上皮化生和异型增生提供了一种潜在的治疗策略,保护了胃黏膜。
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