2. Academic Validation
  3. Metformin inhibits the growth of SCLC cells by inducing autophagy and apoptosis via the suppression of EGFR and AKT signalling

Metformin inhibits the growth of SCLC cells by inducing autophagy and apoptosis via the suppression of EGFR and AKT signalling

  • Sci Rep. 2025 Feb 19;15(1):6081. doi: 10.1038/s41598-025-87537-z.
Hong Xia # 1,  Xue-Jiao Tai # 1,  Wang Cheng # 1,  Yi Wu 2,  Dan He 3,  Li-Feng Wang 3,  Hao Liu 1,  Shen-Yi Zhang 1,  Yu-Ting Sun 1,  Hang-Zhi Liu 1,  Dan-Dan Liu 1,  Hu-Zi Zhao 1,  Fu-Yun Ji 4 5,  Xi-Hua Li 6
Affiliations

Affiliations

  • 1 Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Science, Hubei University of Medicine, 30 Renmin Road, Shiyan, 442000, Hubei, China.
  • 2 Department of Oncology, Taihe Hospital, Hubei University of Medicine, 30 Renmin Road, Shiyan, 442000, Hubei, China.
  • 3 School of Biomedical Engineering, Hubei University of Medicine, 30 Renmin Road, Shiyan, 442000, Hubei, China.
  • 4 Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Science, Hubei University of Medicine, 30 Renmin Road, Shiyan, 442000, Hubei, China. jifuyun@263.net.
  • 5 Yu-Yue Pathology Scientific Research Center, 313 Gaoteng Avenue, Jiulongpo District, Chongqing, 400039, China. jifuyun@263.net.
  • 6 Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Science, Hubei University of Medicine, 30 Renmin Road, Shiyan, 442000, Hubei, China. 20180503@hbmu.edu.cn.
  • # Contributed equally.
PMID: 39971923 DOI: 10.1038/s41598-025-87537-z
Abstract

Small cell lung Cancer (SCLC) is a therapeutically challenging disease. Metformin, an effective agent for the treatment of type 2 diabetes, has been shown to have antitumour effects on many cancers, including non-small cell lung Cancer (NSCLC) and breast Cancer. Currently, the antitumour effects of metformin on SCLC and the underlying molecular mechanisms remain unclear. CCK-8, EdU, colony formation, flow cytometry, immunofluorescence, molecular docking, western blotting, nude mouse transplanted tumour model, and immunohistochemistry experiments were conducted to analyse gene functions and the underlying mechanism involved. In vitro experiments demonstrated that metformin inhibited the growth of SCLC cells (H446, H526, H446/DDP and H526/DDP), which was confirmed in xenograft mouse models in vivo. Additionally, metformin induced cell cycle arrest, Apoptosis, and Autophagy in these SCLC cells. The molecular docking results indicated that metformin has a certain binding affinity for EGFR. The western blotting results revealed that metformin decreased the expression of EGFR, p-EGFR, Akt, and p-AKT, which could be reversed by EGF and SC79. Moreover, metformin activated AMPK and inactivated mTOR, and compound C and SC79 increased the levels of p-mTOR. Metformin can not only enhance the antitumour effect of cisplatin but also alleviate the toxic effects of cisplatin on the organs of xenograft model Animals. In summary, the current study revealed that metformin inhibits the growth of SCLC by inducing Autophagy and Apoptosis via suppression of the EGFR/Akt/AMPK/mTOR pathway. Metformin might be a promising candidate drug for combination therapy of SCLC.

Keywords

Apoptosis; Autophagy; Cell cycle arrest; Metformin; SCLC.

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