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

作　　者：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 

机构地区：[1]Department of Oncology,Guang’anmen Hospital,China Academy of Chinese Medical Sciences,Beijing,100053,China [2]Department of Oncology,Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing,100010,China [3]Department of Cardiology,Guang’anmen Hospital,China Academy of Chinese Medical Sciences,Beijing,100053,China [4]Institute of Traditional Chinese Medicine Information,China Academy of Chinese Medical Sciences,Beijing,100700,China

出　　处：《Chinese Journal of Integrative Medicine》2024年第9期799-808,共10页中国结合医学杂志（英文版）

基　　金：Supported by the Special Scientific Research Project of the Chinese Medicine Industry of the State Administration of Traditional Chinese Medicine of China(No.201307006);National Natural Science Foundation of China(No.82104656,82004179,82074405);Fundamental Research Funds for the Central Public Welfare Research Institutes(No.ZZ14-YQ-013,ZZ15-YQ-024)。

摘　　要：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-1αexpressions in tumor tissue and microvessel density(MVD)was analyzed.Western blot was performed to detect the expression of PI3K/AKT/mTOR/HIF-1αsignaling 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<0.01).Moreover,Scorpiones,Scolopendra and Gekko inhibited the phosphorylation of AKT and ribosomal protein S6 kinase(p70S6K)(P<0.05 or P<0.01).In addition,they also decreased the expression of CD31,MVD,bFGF,TGF-β1 and VEGF compared with the model group(P<0.05 or P<0.01).Conclusion:Scorpiones,Scolopendra and Gekko all showed beneficial effects on lung cancer by ameliorating the hypoxic tumor microenvironment via PI3K/AKT/mTOR/HIF-1αsignaling pathway.

关 键 词：SCORPIONES SCOLOPENDRA Gekko dredging collaterals and activating blood Chinese medicine of worms lung cancer hypoxic tumor microenvironment phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor-1α signaling pathway 

分 类 号：R285.5[医药卫生—中药学]