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敲低MAC30通过抑制Wnt/β-连环蛋白信号通路抑制胃癌增殖并增强其凋亡。

MAC30 Knockdown Inhibits Proliferation and Enhance Apoptosis of Gastric Cancer by Suppressing Wnt/-Cateninsignaling Pathway.

作者信息

Wu Xiaohong, Zhang Yong, Guo Junping, Yan Xun, Shen Li, Zhou Jianping, Zhao Jun, Zhuang Min, Cao Zhihong

机构信息

Department of General Surgery, the Affiliated Yixing Hospital of Jiangsu University, Yixing 214200, China.

Department of Pharmacy, the Affiliated Yixing Hospital of Jiangsu University, Yixing 214200, China.

出版信息

Gastroenterol Res Pract. 2020 Aug 21;2020:6358685. doi: 10.1155/2020/6358685. eCollection 2020.

DOI:10.1155/2020/6358685
PMID:32904598
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7456481/
Abstract

Gastric cancer is one of the most frequently diagnosed cancer and poses a serious threat to health system in the world. Upregulation of meningioma-associated protein (MAC30) has been found in many solid tumors and can regulate the proliferation, differentiation, and apoptosis of different tumor cells. Quantitative polymerase chain reaction (qPCR) was used to detect the expression of MAC30 in 68 patients with gastric cancer and their adjacent tissues. Lentiviral vector pGCSIL-shMAC30-GFP of the RNA interference (RNAi) of the MAC30 gene was transfected into gastric cancer BGC-823 cell line and the expression of lentivirus label protein GFP was observed via fluorescence microscope, while cell proliferation and apoptosis were determined with flow cytometry and MTT assay, respectively. Also, related protein expressions on Wnt/-catenin signaling pathway were analyzed by Western blot method. The expression of MAC30 was abnormally elevated in gastric cancer tissues, while interfering of its expression could significantly inhibit the proliferation of gastric cancer BGC-823 cell line. However, the promotion of apoptosis by mitochondrial pathway was mediated by Bax/Bcl-2 upregulation. Present work showed the effect of downregulated MAC30 expression on proliferation and apoptosis of gastric cancer cell through Wnt/-catenin signaling pathway. Thus, this investigation provides an experimental basis for future development of chemotherapeutic agent on gastric cancer.

摘要

胃癌是最常被诊断出的癌症之一，对全球卫生系统构成严重威胁。在许多实体瘤中都发现脑膜瘤相关蛋白（MAC30）上调，它可调节不同肿瘤细胞的增殖、分化和凋亡。采用定量聚合酶链反应（qPCR）检测68例胃癌患者及其癌旁组织中MAC30的表达。将MAC30基因RNA干扰（RNAi）的慢病毒载体pGCSIL-shMAC30-GFP转染至胃癌BGC-823细胞系，通过荧光显微镜观察慢病毒标记蛋白GFP的表达，同时分别用流式细胞术和MTT法检测细胞增殖和凋亡情况。此外，采用蛋白质印迹法分析Wnt/β-连环蛋白信号通路相关蛋白的表达。MAC30在胃癌组织中表达异常升高，干扰其表达可显著抑制胃癌BGC-823细胞系的增殖。然而，线粒体途径介导的凋亡促进作用是通过上调Bax/Bcl-2实现的。目前的研究表明，下调MAC30表达通过Wnt/β-连环蛋白信号通路对胃癌细胞的增殖和凋亡产生影响。因此，本研究为未来开发胃癌化疗药物提供了实验依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d802/7456481/5592306d0f49/GRP2020-6358685.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d802/7456481/508fcd049964/GRP2020-6358685.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d802/7456481/fb926a2d3b9e/GRP2020-6358685.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d802/7456481/29380a5c1dc6/GRP2020-6358685.003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d802/7456481/1cf28de8543e/GRP2020-6358685.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d802/7456481/5f2c9833816e/GRP2020-6358685.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d802/7456481/5592306d0f49/GRP2020-6358685.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d802/7456481/508fcd049964/GRP2020-6358685.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d802/7456481/fb926a2d3b9e/GRP2020-6358685.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d802/7456481/29380a5c1dc6/GRP2020-6358685.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d802/7456481/d0bb846a0915/GRP2020-6358685.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d802/7456481/437e40c68052/GRP2020-6358685.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d802/7456481/1cf28de8543e/GRP2020-6358685.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d802/7456481/5f2c9833816e/GRP2020-6358685.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d802/7456481/5592306d0f49/GRP2020-6358685.008.jpg

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