AKT抑制剂通过MMP-9/RhoC信号通路和自噬对4nqo诱导的小鼠舌癌的化学预防作用

IF 2.6 4区 医学 Q3 CELL BIOLOGY
Analytical Cellular Pathology Pub Date : 2022-10-05 eCollection Date: 2022-01-01 DOI:10.1155/2022/3770715
Panpan Yin, Jiahui Chen, Yanlin Wu, Feng Gao, Jinlin Wen, Wenbin Zhang, Ying Su, Xinyan Zhang
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引用次数: 1

摘要

口腔癌(OC)是头颈部最常见的癌症,其预后较差,组织病理学上遵循增生、不典型增生和癌症的阶梯模式。在癌前阶段阻断卵巢癌的进展,可大大提高生存率和治愈率。AKT蛋白在癌细胞的信号转导中起着至关重要的作用,我们通过TCGA数据库分析发现AKT在人类OC样品中过表达。因此,本研究旨在探讨AKT抑制剂(MK2206 2HCl)对OC的化学预防作用。在体内,我们建立了4-硝基喹啉-1-氧化物(4NQO-)诱导的小鼠舌癌模型,研究MK2206 2HCl对4NQO致小鼠OC的潜在化学预防作用。结果显示,在4nqo诱导的小鼠舌癌模型中,MK2206 2HCl能显著降低OC的发病率和生长,抑制发育不良向癌的转化,同时显著抑制4nqo诱导的小鼠舌癌细胞增殖、血管生成和肥大细胞(MC)浸润。在体外,我们的研究结果显示,MK2206 2HCl还能抑制口腔鳞状细胞癌(oral squamous cell carcinoma, OSCC)细胞的恶性生物学行为,包括细胞增殖、集落形成、细胞侵袭和迁移,同时促进细胞凋亡。机制研究显示MK2206 2HCl抑制基质金属蛋白酶9 (matrix metalloproteinase 9, MMP-9)和RhoC表达,促进自噬基因LC3 II表达。综上所述,我们的研究结果表明,MK2206 2HCl对4nqo诱导的小鼠舌癌模型具有化学预防作用,其潜在机制可能是通过MMP-9/RhoC信号通路和自噬介导的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Chemoprevention of 4NQO-Induced Mouse Tongue Carcinogenesis by AKT Inhibitor through the MMP-9/RhoC Signaling Pathway and Autophagy.

Chemoprevention of 4NQO-Induced Mouse Tongue Carcinogenesis by AKT Inhibitor through the MMP-9/RhoC Signaling Pathway and Autophagy.

Chemoprevention of 4NQO-Induced Mouse Tongue Carcinogenesis by AKT Inhibitor through the MMP-9/RhoC Signaling Pathway and Autophagy.

Chemoprevention of 4NQO-Induced Mouse Tongue Carcinogenesis by AKT Inhibitor through the MMP-9/RhoC Signaling Pathway and Autophagy.

Oral cancer (OC), the most common cancer in the head and neck, which has a poor prognosis, histopathologically follows a stepwise pattern of hyperplasia, dysplasia, and cancer. Blocking the progression of OC in the precancer stage could greatly improve the survival and cure rates. AKT protein plays a critical role in the signal transduction of cancer cells, and we found that AKT was overexpressed in human OC samples through analysis of TCGA database. Therefore, this study is aimed at investigating the chemopreventive effect of an AKT inhibitor (MK2206 2HCl) on OC. In vivo, we established a 4-nitroquinoline-1-oxide- (4NQO-) induced mouse tongue carcinogenesis model to investigate the potential chemopreventive effect of MK2206 2HCl on mouse OC resulting from 4NQO. The results showed that MK2206 2HCl could significantly reduce the incidence rate and growth of OC, inhibit the transformation of dysplasia to cancer in the 4NQO-induced mouse tongue carcinogenesis model, and simultaneously markedly suppress cell proliferation, angiogenesis, and mast cell (MC) infiltration in 4NQO-induced mouse tongue cancers. In vitro, our results revealed that MK2206 2HCl could also inhibit oral squamous cell carcinoma (OSCC) cell malignant biological behaviors, including cell proliferation, colony formation, cell invasion, and migration, while promoting apoptosis. Mechanistic studies revealed that MK2206 2HCl suppressed matrix metalloproteinase 9 (MMP-9) and RhoC expression and promoted autophagy gene LC3 II expression. In summary, our findings demonstrated the chemopreventive effect of MK2206 2HCl on the 4NQO-induced mouse tongue carcinogenesis model, which likely has an underlying mechanism mediated by the MMP-9/RhoC signaling pathway and autophagy.

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来源期刊
Analytical Cellular Pathology
Analytical Cellular Pathology ONCOLOGY-CELL BIOLOGY
CiteScore
4.90
自引率
3.10%
发文量
70
审稿时长
16 weeks
期刊介绍: Analytical Cellular Pathology is a peer-reviewed, Open Access journal that provides a forum for scientists, medical practitioners and pathologists working in the area of cellular pathology. The journal publishes original research articles, review articles, and clinical studies related to cytology, carcinogenesis, cell receptors, biomarkers, diagnostic pathology, immunopathology, and hematology.
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