n-3 polyunsaturated fatty acids abrogate mTORC1/2 signaling and inhibit adrenocortical carcinoma growth in vitro and in vivo
| Autor: | Meinian Xu, Jun Liu, Zhenguo Chen, Xiaochun Bai, Wei-lie Hu, Bang-Qi Wang, Yong-Bin Zhao, Yukun Wu, Ming Li, Chunping Ao |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Cancer Research Docosahexaenoic Acids Cell Mice Nude Apoptosis mTORC1 Mechanistic Target of Rapamycin Complex 2 Mice SCID Biology Mechanistic Target of Rapamycin Complex 1 behavioral disciplines and activities 03 medical and health sciences Mice 0302 clinical medicine Cell Line Tumor medicine Adrenocortical Carcinoma Animals Humans PI3K/AKT/mTOR pathway Cell Proliferation chemistry.chemical_classification Cell growth TOR Serine-Threonine Kinases Cell Cycle General Medicine Cell cycle Xenograft Model Antitumor Assays Adrenal Cortex Neoplasms Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure nervous system Oncology chemistry Docosahexaenoic acid 030220 oncology & carcinogenesis Multiprotein Complexes Cancer research Female Signal transduction human activities Polyunsaturated fatty acid Signal Transduction |
| Zdroj: | Oncology reports. 35(6) |
| ISSN: | 1791-2431 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|