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Raptor mediates the antiproliferation of cardamonin by mTORC1 inhibition in SKOV3 cells

Authors Shi D, Zhu Y, Niu P, Zhou J, Chen H

Received 24 October 2017

Accepted for publication 28 December 2017

Published 9 February 2018 Volume 2018:11 Pages 757—767

DOI https://doi.org/10.2147/OTT.S155065

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Geoffrey Pietersz


Daohua Shi,* Yanting Zhu,* Peiguang Niu, Jintuo Zhou, Huajiao Chen

Department of Pharmacy, Fujian Provincial Maternity and Children Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China

*These authors contributed equally to this work

Purpose: Cardamonin inhibits the proliferation of SKOV3 cells by suppressing the mammalian target of rapamycin complex 1 (mTORC1). However, the mechanism of cardamonin on mTORC1 inhibition has not been well demonstrated. The regulatory-associated protein of TOR (Raptor) is an essential component of mTORC1. Here, we investigated the role of Raptor in the mTORC1 inhibition effect of cardamonin in SKOV3 cells.
Methods: The expression of Raptor was knockdown by small interfering RNA (siRNA). The expressions of specific binding proteins of mTORC1 were analyzed by Western blotting, and the cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) assay.
Results: Rapamycin, AZD8055, and cardamonin inhibited the activity of mammalian target of rapamycin (mTOR). Different from rapamycin and AZD8055, cardamonin suppressed the phosphorylation and protein expression of Raptor. Transfected with Raptor siRNA, the mTOR activation and proliferation of SKOV3 cells were decreased, and these effects were strengthened by cardamonin in Raptor siRNA SKOV3 cells. Cardamonin interfered with the lysosomal colocalization of mTOR with lysosomal associated membrane protein 2 (LAMP2), which was also hindered by Raptor siRNA. Furthermore, cardamonin strengthened the inhibitory effect on the lysosomal localization of mTOR in Raptor siRNA cells.
Conclusion: Our results suggested that Raptor mainly mediated the inhibition of cardamonin on mTORC1 in SKOV3 cells.

Keywords: cardamonin, Raptor, mTORC1, drug target, ovarian cancer
 

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