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Archives of Gynecology and Obstetrics

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01-09-2018 | Gynecologic Oncology

Orlistat induces apoptosis and protective autophagy in ovarian cancer cells: involvement of Akt-mTOR-mediated signaling pathway

Authors: Hongling Peng, Qiao Wang, Xiaorong Qi, Xi Wang, Xia Zhao

Published in: Archives of Gynecology and Obstetrics | Issue 3/2018

Abstract

Introduction

Orlistat possesses anti-tumor capacity by inducing apoptosis in ovarian cancer cells. However, the mechanism is not clearly understood. Emerging evidence indicates the overlaps between autophagy and apoptosis. In this study, we have investigated the role of autophagy in orlistat-induced apoptosis in ovarian cancer (OC) cells.

Methods

The effect of orlistat on apoptosis was evaluated in SKOV3 and A2780 cell lines by MTT and TUNEL assay. The formations of autophagosomes were observed by acridine orange and GFP-LC3 fluorescence. In addition, conversions of LC3-I to LC3-II were analyzed by western blot, as well as other autophagy-related proteins. 3-Methyladenine (3-MA) was used as an autophagy inhibitor in combined treatment with orlistat. Western blot was further conducted to investigate the molecular mechanisms of orlistat-affected apoptosis and autophagy on protein level.

Results

The proliferation activities of OC cells were inhibited by orlistat in a dose-dependent manner. The expressions of cleaved-caspase 3 and 9 in orlistat-treated cells were increasing, which suggested that orlistat-induced apoptosis was caspase-dependent. At the same time, the average number of GFP-LC3 dots per cell was increased after 48 h of orlistat treatment. The expression levels of LC3-II were significantly up-regulated, as well as other autophagy-related proteins such as Vsp34, Atg7 and UVRAG. These results suggested orlistat-induced autophagy flux, which was further found involved in inhibiting the Akt/mTOR/p70S6K signaling pathway. However, combined treatment of orlistat and 3-MA significantly suppressed the cell viability, which indicated a pro-survival role of autophagy in OC cells.

Conclusion

We suggested that orlistat had anti-cancer effect in OC cells. In addition, autophagy played a pro-survival role, suppressing which the orlistat-induced anti-cancer effect would be more significant.

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Title: Orlistat induces apoptosis and protective autophagy in ovarian cancer cells: involvement of Akt-mTOR-mediated signaling pathway
Authors: Hongling Peng
Qiao Wang
Xiaorong Qi
Xi Wang
Xia Zhao
Publication date: 01-09-2018
Publisher: Springer Berlin Heidelberg
Published in: Archives of Gynecology and Obstetrics / Issue 3/2018
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-018-4841-2

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Orlistat induces apoptosis and protective autophagy in ovarian cancer cells: involvement of Akt-mTOR-mediated signaling pathway

Abstract

Introduction

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

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