Prucalopride Inhibits Proliferation of Ovarian Cancer Cells via Phosphatidylinositol 3-Kinase (PI3K) Signaling Pathway

Abstract

BackgroundOvarian cancer is the second most common malignant tumor of the female reproductive system and is the leading cause of death of gynecological malignancies, but at present there is no effective and safe therapy. There is no previously published report on the anti-cancer effect of prucalopride, which is a high-affinity 5-HT4 receptor. The aim of the present study was to determine whether prucalopride can inhibit proliferation of ovarian cancer cells.Material/MethodsThe cell viability was detected by use of the Cell Counting Kit-8 (CCK-8) assay. The invasion and migration of SKOV3 and OVCAR3 cells was detected by Transwell assay. The cell apoptosis was detected by apoptosis flow detection and Caspase-Glo 3/7 Assay Systems. The apoptosis-related proteins, autophagy marker proteins, and the related-factors of phosphatidylinositol 3-kinase (PI3K) were detected by Western blot.ResultsThe CCK-8 proliferation test showed that prucalopride inhibited the growth of ovarian cancer cell lines SKOV3 and OVCAR3. In the Transwell assay, prucalopride inhibited cell invasion and migration. Furthermore, we found the expression of anti-apoptotic protein Bcl-2 decreased, whereas the expression of pro-apoptotic protein Caspase3 and Bax increased in the SKOV3 cell line treated with prucalopride, as well as cleaved PARP. In addition, the expression of p-AKT, p-mTOR, and p70S6K decreased in the prucalopride-treated group, and the expression of autophagy marker protein LC3-II/I and Beclin1 significantly increased, whereas the expression of p62 protein decreased.ConclusionsThe present study reveals that in ovarian cancer cells, prucalopride inhibits proliferation, migration, and invasion, and induces apoptosis and autophagy, which may be regulated by the PI3K signaling pathway. These results suggest prucalopride has potential as a new drug for clinical ovarian cancer treatment.

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

“…Other work revealed that autophagy was stimulated following the phosphorylation of AKT, the activation of mTor phosphorylation, and the repression of p70S6K, while prucalopride was suggested to hinder the initial step. 11,30 Consistent with this, we found that the inhibition of the PI3K/AKT/mTor signaling pathway contributed to autophagy. Specifically, we observed that the downregulation of p-AKT and p-mTor was accompanied by Beclin 1 reduction and the conversion of LC3.…”

“…10 Liu et al confirmed that prucalopride can inhibit cell behaviors in ovarian cancer. 11 However, it is unknown whether prucalopride could be used to treat lung cancer. Therefore, this study attempted to investigate the antitumor activity of prucalopride in lung cancer cells.…”

<p>Tetramethylpyrazine attenuated bupivacaine-induced neurotoxicity in SH-SY5Y cells through regulating apoptosis, autophagy and oxidative damage</p>

“…Apoptotic cells were detected according to a previously described method. 15 Briefly, SH-SY5Y cells (5×10 5 cells/ well) were seeded to 6-well plates overnight, then treated with BUP (500 μM) and/or TET (200 μM), or BUP+TET +3MA. Cell scraper was used to detach the cells from the culture plate.…”