Abstract
We aimed to determine the effect of ‘Xiaozeng No. 1’ (XZ-1) on cellular apoptosis changes of gastric epithelial dysplasia (GED) and to explore the underlying mechanism. Specimens taken from the pyloric area of the stomachs from rats in each group were subjected to Hematoxylin and Eosin (H&E) staining for pathological examination, TUNEL staining for apoptosis detection, and Western blot analysis for apoptosis-related proteins. The results showed that XZ-1 decreased GED incidence and enhanced gastric epithelial apoptosis. Furthermore, XZ-1 up-regulated the proapoptotic proteins including cleaved caspases (cysteine-dependent aspartate-specific protease) (-3, -8, and -9), Fas, Bax, and Bid, and facilitated the release of cytochrome c from mitochondria to the cytoplasm. Interestingly, XZ-1 enhanced protein expression of NF-κB p65, Ki67, and p53. Moreover, inhibition of NF-κB pathway suppressed the XZ-induced p53 expression, whereas inhibition of NF-κB or p53 pathway suppressed the XZ-induced Ki67. More importantly, inhibition of NF-κB or p53 pathway attenuated the XZ-1-mediated induction of gastric epithelial apoptosis and decline of GED incidence. Collectively, our results demonstrated that XZ-1, almost equivalent effect exerted by the positive control Retin-A, dramatically decreased GED incidence and enhanced gastric epithelial apoptosis. Meanwhile, XZ-1 activated the NF-κB/p53/Ki67-apoptosis signaling pathway, which might be one of the mechanisms whereby XZ-1 reversed GED.
Highlights
Gastric epithelial dysplasia (GED) is an unequivocal neoplastic lesion and is generally accepted as a precursor to gastric adenocarcinomas [1,2]
To explore whether the nulclear factor-kappaB (NF-κB)/Ki67/p53 pathway was involved in the Xiaozeng No 1 (XZ-1)-induced gastric epithelial apoptosis of GED rats, we examined the effect of XZ-1 on protein expression of NF-κB nuclear p65, Ki67, and p53
Our results suggested that the XZ-1-induced cellular apoptosis in the pyloric area of the stomachs from GED rats was attenuated by inhibition of p53 or NF-κB pathway
Summary
Gastric epithelial dysplasia (GED) is an unequivocal neoplastic lesion and is generally accepted as a precursor to gastric adenocarcinomas [1,2]. It is widely known that GED represents the culmination of a chronic inflammation-metaplasia-dysplasia-carcinoma sequence progression [3]. The diagnosis of GED depends on the cytological and architectural abnormalities [1]. GED has been morphologically categorized into adenomatous (or intestinal) and foveolar (or gastric) types [1,4]. On the basis of the severity of histological abnormalities, GED has been graded either as low and high grade dysplasia or as mild, moderate, and severe dysplasia [5,6,7]. The prevalence of GED reveals wide geographic differences, with incidence rates ranging from 0.5 to 3.8% in Western population but rates from 9.0 to 20.0% in regions such as Colombia and China [4,8,9]. The clinical significance of GED has been stressed because of the establishment of its close association with the risk of gastric cancer [1]
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