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沙利霉素和17-AAG对人胃癌细胞体外增殖的影响。

Effects of salinomycin and 17‑AAG on proliferation of human gastric cancer cells in vitro.

作者信息

Zhang Zuwen, Zhao Jumei, Mi Zhikuan, Pang Qiuxia, Wang Aihong, Chen Meini, Liu Xiaobin, Wei Xiaoli, Liu Tao

机构信息

Key Laboratory of Cancer Prevention and Control, Yan'an University, Yan'an, Shanxi 716000, P.R. China.

The First Ward of Department of Otolaryngology, The Affiliated Hospital of Yan'an University, Yan'an, Shanxi 716000, P.R. China.

出版信息

Mol Med Rep. 2017 Aug;16(2):1063-1070. doi: 10.3892/mmr.2017.6735. Epub 2017 Jun 9.

Abstract

The aim of the present study was to investigate the effects and mechanisms of 17‑AAG combined with salinomycin treatment on proliferation and apoptosis of the SGC‑7901 gastric cancer cell line. An MTT assay was used to detect the proliferation of SGC‑7901 cells. Morphological alterations of cells were observed under inverted phase‑contrast and fluorescence microscopes. Cell cycle and apoptosis were assessed by flow cytometry analysis. The protein expression of nuclear factor (NF)‑κB p65 and Fas‑ligand (L) were evaluated by immunocytochemistry. Salinomycin with a concentration range of 1‑32 µmol/l was demonstrated to inhibit growth of SGC‑7901 cells effectively, affect the morphology and apoptosis rate of cells, and arrest SGC‑7901 cells in S phase. Furthermore, salinomycin significantly increased the protein expression of Fas‑L and decreased the protein expression of NF‑κB p65. The alterations in SGC‑7901 cells co‑treated with salinomycin and 17‑AAG were more significant compared with cells treated with one drug only. In conclusion, the individual use of salinomycin and combined use with 17‑AAG may significantly inhibit SGC‑7901 gastric cancer cell proliferation and induce cell apoptosis. The potential mechanisms may be associated with upregulation of Fas‑L and downregulation of NF‑κB. These results provide a basis for the potential use of salinomycin in gastric cancer treatment.

摘要

本研究的目的是探讨17-AAG联合沙利霉素处理对SGC-7901胃癌细胞系增殖和凋亡的影响及机制。采用MTT法检测SGC-7901细胞的增殖情况。在倒置相差显微镜和荧光显微镜下观察细胞的形态学改变。通过流式细胞术分析评估细胞周期和凋亡情况。采用免疫细胞化学法评估核因子(NF)-κB p65和Fas配体(L)的蛋白表达。浓度范围为1-32 μmol/l的沙利霉素被证明能有效抑制SGC-7901细胞的生长,影响细胞的形态和凋亡率,并使SGC-7901细胞停滞于S期。此外,沙利霉素显著增加Fas-L的蛋白表达,降低NF-κB p65的蛋白表达。与仅用一种药物处理的细胞相比,沙利霉素和17-AAG联合处理的SGC-7901细胞的改变更显著。总之,单独使用沙利霉素以及与17-AAG联合使用可能显著抑制SGC-7901胃癌细胞的增殖并诱导细胞凋亡。潜在机制可能与Fas-L的上调和NF-κB的下调有关。这些结果为沙利霉素在胃癌治疗中的潜在应用提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88ae/5562019/2eaa3eac45e6/MMR-16-02-1063-g00.jpg

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