Aim: Gastric cancer is a leading cause of cancer death worldwide. In-depth research of precancerous lesions of gastric carcinoma (PLGC) with malignant transformation potential is a key measure to prevent the development of gastric carcinoma. Recently, calycosin has been shown to have anticancer effects in vitro and in vivo. The molecular mechanism by which calycosin affects PLGC, however, has not yet been elucidated. The purpose of this study was to evaluate the effect and mechanism of calycosin in N‐methyl‐Nʹ‐nitro‐N‐nitrosoguanidine (MNNG)-induced PLGC rats.
Methods: The effects of calycosin in the gastric mucosa of rats with PLGC were evaluated using histopathology and transmission electron microscopy (TEM). For further characterization, the expression levels of integrin β 1, nuclear factor kappa B (NF-κB), p-NF-κB, DARPP-32 and signal transducer and activator of transcription 3 (STAT3) were determined by Western blot assay and immunohistochemistry.
Results: Hematoxylin–eosin and high iron diamine–Alcian blue–periodic acid-Schiff (HID-AB-PAS) staining showed that intestinal metaplasia and dysplasia were significantly ameliorated in the calycosin intervention groups compared with the model group. Further, TEM results showed that calycosin intervention tempered microvascular abnormalities and cell morphology of primary and parietal cells in PLGC tissues. The results suggested that calycosin had gastro-protective effects in MNNG-induced PLGC rats. Western blot and immunohistochemistry analysis showed that the increased protein expression levels of NF-κB, p-NF-κB, DARPP-32 and STAT3 in the model group were downregulated by calycosin. The upregulation of integrin β 1 expression induced by MNNG was decreased in the calycosin groups.
Conclusion: Collectively, calycosin protected against gastric mucosal injury in part via regulation of the integrin β 1/NF-κB/DARPP-32 pathway and suppressed the expression of STAT3 in PLGC. The elucidation of this effect and mechanism of calycosin in PLGC provides a potential therapeutic strategy for treatment of gastric precancerous lesions.

Keywords: precancerous lesions of gastric carcinoma, calycosin, inflammation, angiogenesis, gastric mucosa protection


中文翻译：

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Calycosin对大鼠胃癌癌前病变的保护作用。

目的：胃癌是全球癌症死亡的主要原因。深入研究具有恶变潜能的胃癌前病变（PLGC）是预防胃癌发展的关键措施。最近，花萼素已被证明在体外和体内具有抗癌作用。然而，花萼素影响 PLGC 的分子机制尚未阐明。本研究的目的是评估毛蕊花素在N-甲基-N-硝基-N-亚硝基胍(MNNG) 诱导的 PLGC 大鼠中的作用和机制。
方法：使用组织病理学和透射电子显微镜 (TEM) 评估 PLGC 大鼠胃黏膜中花萼苷的作用。为了进一步表征，通过蛋白质印迹法和免疫组织化学测定整合素 β 1、核因子 kappa B (NF-κB)、p-NF-κB、DARPP-32 和信号转导和转录激活因子 3 (STAT3) 的表达水平.
结果：苏木精-伊红和高铁二胺-阿尔新蓝-高碘酸-希夫（HID-AB-PAS）染色显示，与模型组相比，花萼素干预组的肠化生和不典型增生明显改善。此外，TEM 结果表明，花萼苷干预缓和了 PLGC 组织中原代细胞和壁细胞的微血管异常和细胞形态。结果表明，毛蕊花素对 MNNG 诱导的 PLGC 大鼠具有胃保护作用。Western blot和免疫组化分析显示，模型组NF-κB、p-NF-κB、DARPP-32和STAT3蛋白表达水平升高被毛蕊花素下调。MNNG 诱导的整合素 β 1 表达上调在花萼素组中降低。
结论：总的来说，花萼素部分通过调节整合素 β 1/NF-κB/DARPP-32 通路来保护胃粘膜损伤，并抑制 PLGC 中 STAT3 的表达。对 PLGC 中 calycosin 的这种作用和机制的阐明为治疗胃癌前病变提供了潜在的治疗策略。

Keywords:胃癌癌前病变, calycosin, 炎症, 血管生成, 胃黏膜保护