n-3 polyunsaturated fatty acids abrogate mTORC1/2 signaling and inhibit adrenocortical carcinoma growth in vitro and in vivo

Liu,Jun; Xu,Meinian; Zhao,Yongbin; Ao,Chunping; Wu,Yukun; Chen,Zhenguo; Wang,Bangqi; Bai,Xiaochun; Li,Ming; Hu,Weilie

doi:10.3892/or.2016.4720

n-3 polyunsaturated fatty acids abrogate mTORC1/2 signaling and inhibit adrenocortical carcinoma growth in vitro and in vivo

Authors:
- Jun Liu
- Meinian Xu
- Yongbin Zhao
- Chunping Ao
- Yukun Wu
- Zhenguo Chen
- Bangqi Wang
- Xiaochun Bai
- Ming Li
- Weilie Hu
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Affiliations: Department of Urology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, P.R. China, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, P.R. China
Published online on: March 31, 2016 https://doi.org/10.3892/or.2016.4720
Pages: 3514-3522

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Abstract

n-3 polyunsaturated fatty acids (PUFAs) are essential for human health and have been reported to reduce the risk of cancer, inhibit the growth of various types of tumors both in vitro and in vivo, and affect adrenal function. However, their effects on adrenocortical carcinoma (ACC) are not known. In the present study, we demonstrated that docosahexenoic acid (DHA) inhibited ACC cell proliferation, colony formation and cell cycle progression, and promoted apoptosis. In addition, ectopic expression of fat-1, a desaturase that converts n-6 to n-3 PUFAs endogenously, also inhibited ACC cell proliferation. Moreover, supplementing n-3 PUFAs in the diet efficiently prevented ACC cell growth in xenograft models. Notably, implanted ACC cells were unable to grow in fat-1 transgenic severe combined immune deficiency mice. Further study revealed that exogenous and endogenous n-3 PUFAs efficiently suppressed both mTOR complex 1 (mTORC1) and mTORC2 signaling in ACC in vitro and in vivo. Taken together, our findings provide comprehensive preclinical evidence that n-3 PUFAs efficiently prevent ACC growth by inhibiting mTORC1/2, which may have important implications in the treatment of ACC.

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