Prucalopride Inhibits Proliferation of Ovarian Cancer Cells via Phosphatidylinositol 3-Kinase (PI3K) Signaling Pathway
Authors: Ting Liu
Lu Zhang
Hui Zhang
Xiaolin Liu
Yintao Xu
Journal: Medical Science Monitor (2018)
Discipline: CLINICAL MEDICINE
Keywords: Ovarian cancer; Prucalopride; Proliferation; Migration; Invasion
Affiliations: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong, China (mainland).

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. 

Retracted: No

PubPeer comments:
 This article was reviewed on the error bar podcast episode 3: https: theerrorbar.com ?e=3. The slightly-edited transcript is copied here: headline: LOVE IS IN THE (UNDERARM H)AIR tweet: the brains of 18 single young men seem to distinguish between the armpit smells of 5 similar-age ovulating women the smells of an older group of 5 pregnant women. why we need to know this is anyone s guess. description: the most remarkable thing about this story is that it did NOT appear in any of the newspapers this week. yet this study is tabloid gold. i am starting to wonder whether science journalists check pubmed every week like the error bar does. somewhere in Aachen, Germany, 5 ovulating and 5 pregnant women had 2 nights worth of their underarm sweat mopped up and refrigerated. these sweatpads were then placed under the noses of 18 young, single, heterosexual, cisgender men in a brain scanner while they looked at pictures of women s faces. after inhaling the sweat for 3.5s, the single men rated the attractiveness of the pictures, or they guessed whether the depicted woman was pregnant or not (it was not mentioned if the women in this standard image database were pregnant or not). the young men s attractiveness ratings or pregnancy guesses did not differ substantially after smelling the ovulating women s sweat compared to the pregnant women s or to a neutral one. but the brain did seem to distinguish the women s armpits: after smelling the ovulating women s sweat, several regions in the, [checks notes], medial orbitofrontal cortex responded more than for the pregnant womens pits. evaluation: the study seems to be a fairly standard, well-conducted brain imaging experiment - there s nothing obviously amiss in the methods or analysis, and the authors have been quite honest in laying out their hypotheses and finding that most of them were not supported. so yes, on the face of it, the brain s orbitofrontal cortex - which seems to be the error bar s favourite brain area - does seem to distinguish between the sweats of ovulating and pregnant women. while there were no strong differences in the attractiveness ratings of the photographs under the different smell conditions - photos were rated an average of 6 on the scale - the differences between conditions were in the hypothesised direction, so the behavioural part of this study may have been a bit underpowered. the only obvious caveat about the study is that the 5 ovulating women who provided sweat were an average age of 24, while the 5 pregnant women were an average of 30 - and this is a substantial statistical difference. why such an obvious confound was not controlled in this expensive, quite invasive study, is not known. perhaps the brain can smell the age, rather than ovulation? as for the brain imaging part: the error bar finds it intriguing that in the last episode the orbitofrontal and medial prefrontal cortex were associated with learning about reward, and in this episode it is associated with the perception of beauty in a meta-analysis of 49 studies, and the difference between ovulating and pregnant women in a single sweat-smelling study. i think we ve found St Valentines brain area. let s hope the British tabloids do not find this study. conclusion: single young men s brains seem to distinguish between the smells of a group of similarly-aged ovulating women the smells of an older group of pregnant women. science is a little bit larger now, but perhaps not much better. ,