Scorpiones, Scolopendra and Gekko Inhibit Lung Cancer Growth and Metastasis by Ameliorating Hypoxic Tumor Microenvironment via PI3K/AKT/mTOR/HIF-1α Signaling Pathway

• Published in: Chinese journal of integrative medicine 2024-09, Vol.30 (9), p.799-808
• Main Authors: Mao, Qi-yuan, Wang, Xue-qian, Lin, Fei, Yu, Ming-wei, Fan, Hui-ting, Zheng, Qi, Liu, Lan-chun, Zhang, Chu-chu, Li, Dao-rui, Lin, Hong-sheng
• Format: Article
• Language: English
• Subjects: Animals; Cell Line, Tumor; Cell Proliferation - drug effects; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Neovascularization, Pathologic; Original Article; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; TOR Serine-Threonine Kinases - metabolism; Tumor Hypoxia - drug effects; Tumor Microenvironment - drug effects
• ISSN: 1672-0415; 1993-0402; 1993-0402
• DOI: 10.1007/s11655-024-3803-8

Objective To investigate whether Buthus martensii karsch (Scorpiones), Scolopendra subspinipes mutilans L. Koch (Scolopendra) and Gekko gecko Linnaeus (Gekko) could ameliorate the hypoxic tumor microenvironment and inhibit lung cancer growth and metastasis by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor-1α (PI3K/AKT/mTOR/HIF-1α) signaling pathway. Methods Male C57BL/6J mice were inoculated with luciferase labeled LL/2-luc-M38 cell suspension to develop lung cancer models, with rapamycin and cyclophosphamide as positive controls. Carboxy methyl cellulose solutions of Scorpiones, Scolopendra and Gekko were administered intragastrically as 0.33, 0.33, and 0.83 g/kg, respectively once daily for 21 days. Fluorescent expression were detected every 7 days after inoculation, and tumor growth curves were plotted. Immunohistochemistry was performed to determine CD31 and HIF-1α expressions in tumor tissue and microvessel density (MVD) was analyzed. Western blot was performed to detect the expression of PI3K/AKT/mTOR/HIF-1α signaling pathway-related proteins. Enzyme-linked immunosorbent assay was performed to detect serum basic fibroblast growth factor (bFGF), transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF) in mice. Results Scorpiones, Scolopendra and Gekko prolonged the survival time and inhibited lung cancer metastasis and expression of HIF-1α (all P