Down-Regulation of SREBP via PI3K/AKT/mTOR Pathway Inhibits the Proliferation and Invasion of Non-Small-Cell Lung Cancer Cells

• Main Authors: Zhang B, Wu J, Guo P, Wang Y, Fang Z, Tian J, Yu Y, Teng W, Luo Y, Li Y
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-09-01
• Series: OncoTargets and Therapy
• Subjects: non-small-cell lung cancer; srebp; proliferation; invasion; pi3k/akt/mtor.
• Online Access: https://www.dovepress.com/down-regulation-of-srebp-via-pi3kaktmtor-pathway-inhibits-the-prolifer-peer-reviewed-article-OTT

Bo Zhang,1,* Jianchun Wu,1,* Peng Guo,1 Yi Wang,2 Zhihong Fang,1 Jianhui Tian,3 Yongchun Yu,4 Wenjing Teng,1 Yingbin Luo,1 Yan Li1 1Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, People’s Republic of China; 2Department of Pathology, Caner Hospital Affiliated Zhengzhou University, Henan, Zhengzhou 450008, People’s Republic of China; 3Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, People’s Republic of China; 4Institute for Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Li; Yingbin LuoDepartment of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, 274 Middle Zhijiang Rode, Shanghai, People’s Republic of ChinaEmail [e-mail]; [e-mail]: Lung cancer is one of the most common causes of cancer-related deaths worldwide, metabolic disorders are also a problem that puzzles mankind. SREBP is overexpressed in non-small-cell lung cancer (NSCLC) and is also a key regulator of lipid synthesis. However, the mechanisms by which SREBP regulates the proliferation, migration and invasion in NSCLC remain unclear.Materials and Methods: CCK-8, colony formation assay, soft agar assay, scratch wound healing assay and transwell assays were performed to detect proliferation, and invasion in NSCLC cells, respectively. In addition, Western blotting assay, qPCR and immunofluorescence were applied to detect the expressions of SREBP1, SREBP2, ki-67, PCNA, Bax, bcl-2, E-cadherin, N-cadherin, Vimentin, PI3K, p-PI3k, AKT, p-AKT, mTOR, p-mTOR in NSCLC cells.Results: In this study, downregulation of SREBP significantly inhibited the proliferation, migration and invasion of A549 and H1299 cells. Moreover, the method of piecewise inhibition was adopted to prove that SREBP is a downstream molecule of the PI3K/Akt/mTOR signaling pathway.Conclusion: Our study indicated that downregulation of SREBP inhibited the growth in NSCLC cells via PI3K/AKT/mTOR signaling pathway. Thus, we suggested SREBP may serve as a potential target for the treatment of patients with NSCLC.Keywords: non-small-cell lung cancer, SREBP, proliferation, invasion, PI3K/AKT/mTOR