Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Jun 17:24:4137-4145.
doi: 10.12659/MSM.907853.

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

Xiaolin Liu  1 , Yintao Xu  1 , Lu Zhang  1 , Ting Liu  1 , Hui Zhang  1
Affiliations

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

Xiaolin Liu et al. Med Sci Monit. .

Abstract

BACKGROUND Ovarian 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 AND METHODS The 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. RESULTS The 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. CONCLUSIONS The 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.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest

None.

Figures

Figure 1
Figure 1
Effect of prucalopride on SKOV3 and OVCAR3 cell proliferation by CCK-8 assay. (A) SKOV3 cells were treated with prucalopride (0.1, 1, 10 μM) for different lengths of time (24, 48, 72 h). (B) OVCAR3 cells were treated with prucalopride (0.1, 1, 10 μM) for the same different time points. * P<0.05 compared with NC group.
Figure 2
Figure 2
Prucalopride inhibits SKOV3 and OVCAR3 cell invasion and migration. (A, C) The images show the invasion and migration ability of SKOV3 and OVCAR3 cells stained by crystal violet. Images were captured using an inverted microscope with ×100 magnification. (B, D) The invading and migrating cells are shown by quantification. * P<0.05 compared with NC group.
Figure 3
Figure 3
Prucalopride induces SKOV3 cell apoptosis as shown by morphological changes and Annexin V-FITC/PI staining assay. (A) Morphological changes in SKOV3 cells treated with prucalopride, including cell shrinkage, increased brightness, and detachment from the substratum. (B) The apoptosis of SKOV3 cells (treated with prucalopride for 24 h) was analyzed by Annexin V-FITC and PI, illustrated by representative flow charts and quantification. (C) The quantification results were showed. * P<0.05 compared with NC group.
Figure 4
Figure 4
Prucalopride induces SKOV3 cell apoptosis as shown by Caspase-Glo 3/7 assay and Western blot analysis. (A) Prucalopride-treated cells had a significant increase in caspase 3/7 activity. (B, C) Western blot analysis of SKOV3 cells treated with prucalopride for 24 h. The band intensities were quantified. The results were all normalized to the GAPDH loading control. (D–G) Relative protein levels of apoptosis-related protein. * P<0.05 compared with NC group.
Figure 5
Figure 5
Effects of prucalopride on the PI3K signaling pathway in SKOV3 cells. (A) Expression levels of AKT, p-AKT, mTOR, p-mTOR, and p70S6K were measured in the SKOV3 cell treatment with prucalopride using Western blot analysis. (B–F) The relative protein levels of AKT, p-AKT, mTOR, p-mTOR, and p70S6K. * P<0.05 compared with NC group.
Figure 6
Figure 6
Prucalopride promotes autophagy of ovarian cancer cell SKOV3. (A) Expression levels of LC3-II, Beclin1, and p62 were measured in the SKOV3 cells treated with prucalopride using Western blot analysis. (B–D) The relative protein levels of LC3-II, Beclin1, and p62. * P<0.05 compared with NC group.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Worzfeld T, Pogge von Strandmann E, Huber M, et al. The unique molecular and cellular microenvironment of ovarian cancer. Front Oncol. 2017;7:24. - PMC - PubMed
    1. Yeung TL, Leung CS, Li F, et al. Targeting stromal-cancer cell crosstalk networks in ovarian cancer treatment. Biomolecules. 2016;6:3. - PMC - PubMed
    1. Yan B, Yin F, Wang QI, et al. Integration and bioinformatics analysis of DNA-methylated genes associated with drug resistance in ovarian cancer. Oncol Lett. 2016;12:157–66. - PMC - PubMed
    1. Faber MT, Kjaer SK, Dehlendorff C, et al. Cigarette smoking and risk of ovarian cancer: A pooled analysis of 21 case-control studies. Cancer Causes Control. 2013;24:989–1004. - PMC - PubMed
    1. Weidle UH, Birzele F, Kollmorgen G, Rueger R. Mechanisms and targets involved in dissemination of ovarian cancer. Cancer Genomics Proteomics. 2016;13:407–23. - PMC - PubMed

MeSH terms