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视网膜母细胞瘤结合蛋白 4 的过表达通过抑制磷脂酰肌醇 3-激酶/蛋白激酶 B 通路促进 AGS 胃癌细胞的放射敏感性。

Overexpression of retinoblastoma‑binding protein 4 contributes to the radiosensitivity of AGS gastric cancer cells via phosphoinositide3‑kinase/protein kinase B pathway suppression.

机构信息

Laboratory Department, Jingmen No. 1 People's Hospital, Jingmen, Hubei 448000, P.R. China.

Department of Hematology, Jingmen No. 1 People's Hospital, Jingmen, Hubei 448000, P.R. China.

出版信息

Mol Med Rep. 2018 Aug;18(2):1571-1581. doi: 10.3892/mmr.2018.9153. Epub 2018 Jun 11.

Abstract

In the present study, the effects and underlying mechanism of RbAp48 on the radiosensitivity of AGS gastric cancer cells was investigated. Cell proliferation was determined with an MTT assay. Flow cytometry was performed to evaluate the cell cycle and apoptosis. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were performed to detect mRNA and protein expression, respectively, including RbAp48, phosphoinositide 3‑kinase (PI3K) and protein kinase B (Akt). The results revealed that radiation enhanced the expression level of RbAp48 in AGS cells, and that RbAp48 combined with radiation reduced AGS cell proliferation. In addition, RbAp48 combined with radiation resulted in G2 phase arrest and induced apoptosis via regulation of the PI3K/Akt pathway. In conclusion, it was demonstrated that overexpression of RbAp48 enhanced the radiosensitivity of AGS gastric cancer cells via suppression of PI3K/Akt pathway activity, suggesting that RbAp48 may hold potential as a gene therapeutic strategy in the future, aiding in the treatment of gastric cancer.

摘要

在本研究中,研究了 RbAp48 对 AGS 胃癌细胞放射敏感性的作用及其潜在机制。采用 MTT 法测定细胞增殖。通过流式细胞术评估细胞周期和凋亡。采用逆转录-定量聚合酶链反应和 Western blot 分析分别检测 RbAp48、磷酸肌醇 3-激酶(PI3K)和蛋白激酶 B(Akt)的 mRNA 和蛋白表达。结果显示,辐射增强了 AGS 细胞中 RbAp48 的表达水平,而 RbAp48 与辐射结合可降低 AGS 细胞增殖。此外,RbAp48 与辐射结合导致 G2 期阻滞,并通过调节 PI3K/Akt 通路诱导细胞凋亡。综上所述,结果表明,RbAp48 的过表达通过抑制 PI3K/Akt 通路活性增强了 AGS 胃癌细胞的放射敏感性,提示 RbAp48 可能具有作为未来基因治疗策略的潜力,有助于胃癌的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bd1/6072197/b4beb09c4775/MMR-18-02-1571-g00.jpg

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