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普芦卡必利通过阻断 PI3K/AKT/mTor 信号通路抑制肺癌细胞增殖、侵袭和迁移。

Prucalopride inhibits lung cancer cell proliferation, invasion, and migration through blocking of the PI3K/AKT/mTor signaling pathway.

机构信息

Department of Respiratory Medicine, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.

Department of Geriatrics, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.

出版信息

Hum Exp Toxicol. 2020 Feb;39(2):173-181. doi: 10.1177/0960327119883409. Epub 2019 Oct 22.

DOI:10.1177/0960327119883409
PMID:31640407
Abstract

Lung cancer is the main cause of cancer incidence and mortality around the world. Prucalopride is an agonist for the 5-hydroxytryptamine 4 receptor, but it was unknown whether prucalopride could be used to treat lung cancer. To investigate the biological effects of prucalopride on proliferation, apoptosis, invasion, and migration of lung cancer cells, and its underlying molecular mechanism in the progression of lung cancer, we performed this study. The Cell Counting Kit 8 assay was used to measure the proliferation of A549/A427 lung cancer cells treated with prucalopride. Transwell assay was applied to evaluate cell invasion and migration. Cell apoptosis was detected by flow cytometry and Western blot analyses. The expression levels of related proteins in the PI3K/AKT/mTor signaling pathway were analyzed by Western blotting. Prucalopride inhibited the proliferation, invasion, and migration of A549/A427 human lung cancer cells. It also induced autophagy and apoptosis and decreased the expression of the phosphorylated protein kinase B (AKT) and mammalian target of rapamycin (mTor) in these cells. This study implied an inhibitory role for prucalopride in the progression of human lung cancer.

摘要

肺癌是全世界癌症发病率和死亡率的主要原因。普芦卡必利是 5-羟色胺 4 受体激动剂,但尚不清楚普芦卡必利是否可用于治疗肺癌。为了研究普芦卡必利对肺癌细胞增殖、凋亡、侵袭和迁移的生物学影响及其在肺癌进展中的潜在分子机制,我们进行了这项研究。使用细胞计数试剂盒 8 检测普芦卡必利处理的 A549/A427 肺癌细胞的增殖情况。采用 Transwell 测定法评估细胞侵袭和迁移。通过流式细胞术和 Western blot 分析检测细胞凋亡。通过 Western blot 分析检测 PI3K/AKT/mTor 信号通路中相关蛋白的表达水平。普芦卡必利抑制 A549/A427 人肺癌细胞的增殖、侵袭和迁移。它还诱导自噬和细胞凋亡,并降低这些细胞中磷酸化蛋白激酶 B(AKT)和雷帕霉素靶蛋白(mTor)的表达。这项研究表明普芦卡必利在人肺癌进展中具有抑制作用。

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