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迷迭香酸类似物-11通过表皮生长因子受体(EGFR)/蛋白激酶B(Akt)/核因子κB(NF-κB)信号通路诱导人胃癌SGC-7901细胞凋亡。

Rosmarinic Acid Analogue-11 Induces Apoptosis of Human Gastric Cancer SGC-7901 Cells via the Epidermal Growth Factor Receptor (EGFR)/Akt/Nuclear Factor kappa B (NF-κB) Pathway.

作者信息

Li Wanting, Li Qing, Wei Liqun, Pan Xiaohang, Huang Daohang, Gan Jialiang, Tang Shuangyi

机构信息

Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland).

College of Pharmacy, Guangxi Medical University, Nanning, Guangxi, China (mainland).

出版信息

Med Sci Monit Basic Res. 2019 Feb 25;25:63-75. doi: 10.12659/MSMBR.913331.

Abstract

BACKGROUND According to the latest statistics from the American Cancer Society, there will be 1.73 million cancer cases and more than 600 000 cancer deaths in the United States in 2018, among which there will be 26 240 new cases of gastric cancer and around 10 800 deaths arising from gastric cancer. The objective of this study was to use RAA-11 to intervene in SGC-7901 cells to understand its effects on cell proliferation and apoptosis, and to explore the apoptosis mechanism. MATERIAL AND METHODS MTT assay was used to detect the survival of human gastric mucosal epithelial GES-1 cells and human gastric cancer SGC-7901 cells. Colony formation assay was used to observe the colony forming ability in SGC-7901 cells. The apoptotic rate of SGC-7901 cells was evaluated by Hoechst33258 staining and flow cytometry. qRT-PCR was used to analyze the epidermal growth factor receptor (EGFR) mRNA expression level in SGC-7901 cells. Western blot was used to examine the expression levels of caspase-3, Bcl-2, BAX, EGFR, Akt, p-Akt, and NF-κB in SGC-7901 cells. RESULTS RAA-11 is capable of inhibiting the proliferation and inducing the apoptosis of SGC-7901 cells in a time- and dose-dependent manner. Western blot showed that the expression levels of caspase-3 and BAX were upregulated, while the expression levels of Bcl-2, EGFR, Akt, p-Akt, and NF-κB in the SGC-7901 cells were downregulated. CONCLUSIONS Apoptosis can be induced in SGC-7901 cells by RAA-11, potentially via the EGFR/Akt/NF-κB pathway, indicating that RAA-11 might be a potent agent for cancer treatment.

摘要

背景 根据美国癌症协会的最新统计数据,2018年美国将有173万例癌症病例和超过60万例癌症死亡病例,其中将有26240例胃癌新发病例,约10800例胃癌死亡病例。本研究的目的是使用RAA - 11干预SGC - 7901细胞,了解其对细胞增殖和凋亡的影响,并探讨凋亡机制。

材料与方法 采用MTT法检测人胃黏膜上皮GES - 1细胞和人胃癌SGC - 7901细胞的存活率。采用集落形成试验观察SGC - 7901细胞的集落形成能力。通过Hoechst33258染色和流式细胞术评估SGC - 7901细胞的凋亡率。采用qRT - PCR分析SGC - 7901细胞中表皮生长因子受体(EGFR)mRNA表达水平。采用蛋白质免疫印迹法检测SGC - 7901细胞中caspase - 3、Bcl - 2、BAX、EGFR、Akt、p - Akt和NF - κB的表达水平。

结果 RAA - 11能够以时间和剂量依赖性方式抑制SGC - 7901细胞的增殖并诱导其凋亡。蛋白质免疫印迹法显示,SGC - 7901细胞中caspase - 3和BAX的表达水平上调,而Bcl - 2、EGFR、Akt、p - Akt和NF - κB的表达水平下调。

结论 RAA - 11可能通过EGFR/Akt/NF - κB途径诱导SGC - 7901细胞凋亡,表明RAA - 11可能是一种有效的癌症治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a5/6404632/fe0ff588b7cc/medscimonitbasicres-25-63-g001.jpg

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