IL-37 induces autophagy in hepatocellular carcinoma cells by inhibiting the PI3K/AKT/mTOR pathway |
| |
| Affiliation: | 1. Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, 110001, PR China;2. Department of Orthopedic Surgery, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, 110001, PR China;1. Plasma Life Science, Leibniz Institute for Plasma Science and Technology (INP Greifswald), Greifswald, Germany;2. Center for Innovation Competence (ZIK) Plasmatis, Greifswald, Germany;1. Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Gyounggi-Do, Republic of Korea;2. Department of Electrical and Computer Engineering, Ajou University, Suwon, Gyounggi-Do, Republic of Korea;3. Department of Molecular Science and Technology and Department of Life Science, Ajou University, Suwon, Gyounggi-Do, Republic of Korea;4. Department of Otolaryngology-Head and Neck Surgery, Yonsei University Wonju College of Medicine, Wonju, Gangwon-Do, Republic of Korea;5. PSM America Inc., Colorado Springs, CO, USA;1. Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA;2. Division of Hematology-Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA;3. Division of Genetics, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA;4. Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA;5. Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA;6. Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA;7. Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02215, USA;8. Cancer Metabolism DPU, GlaxoSmithKline, Collegeville, PA 19426, USA;9. Center for Regulatory and Environmental Analytical Metabolomics;10. Department of Surgery, University of Louisville, Louisville, KY 40208, USA;1. College of Pharmacy, The Ohio State University, Columbus, OH, United States;2. College of Pharmacy, University of Florida, Gainesville, FL, United States |
| |
| Abstract: | Autophagy is an intracellular “self-eating” process that is closely related to inflammation and cellular immunity. New studies indicate that autophagy is also involved in tumor suppression. The anti-inflammatory cytokine interleukin-37 (IL-37) has been shown to have tumor-suppressive abilities in hepatocellular carcinoma (HCC). Notably, autophagy appears to play a dual role in the development of HCC and may be involved in both tumorigenesis and tumor suppression. However, the potential role of IL-37 in autophagy is currently unknown. In this study, we investigated the effect of IL-37 on autophagy in multiple HCC cell lines. In doing so, we found that IL-37 inhibits proliferation in HCC cells and also induces autophagy and apoptosis in the SMMC-7721 and Huh-7 cell lines. Further experiments revealed that IL-37 treatment reduced the levels of phosphorylated protein kinase B (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), phosphorylated p70 ribosomal protein s6 kinase (p-p70S6K) and phosphorylated 4E-binding protein 1 (4E-BP1). Moreover, treatment with an AKT agonist, insulin-like growth factor 1 (IGF-1), reversed these IL-37-mediated effects on autophagy, and treatment with an phosphoinositide-3-kinase (PI3K)/AKT inhibitor, LY294002, mimicked the effects of IL-37. Taken together, these results indicate that IL-37 regulates autophagy in SMMC-7721 and Huh-7 cells via inhibition of the PI3K/AKT/mTOR signaling pathway. |
| |
| Keywords: | Autophagy IL-37 Phosphorylated protein kinase B Mammalian target of rapamycin |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
