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

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外文摘要：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-1 α(PI3K/AKT/mTOR/HIF-1 α)signaling pathway.Methods:Male C57BU6J mice were inoculated with luciferase labeled LU2-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-1 α expressions in tumor tissue and microvessel density(MVD)was analyzed.Western blot was performed to detect the expression of PI3K/AKT/mTOR/HIF-1 α signaling pathway-related proteins.Enzyme-linked immunosorbent assay was performed to detect serum basic fibroblast growth factor(bFGF),transforming growth factor-β 1(TGF-β 1)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-1 α(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-β 1 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-1 α signaling pathway.

外文关键词：

ScorpionesScolopendraGekkodredging collaterals and activating bloodChinese medicine of wormslung cancerhypoxic tumor microenvironmentphosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor-1 αsignaling path

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

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作者单位：

Department of Oncology,Guang'anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China

Department of Oncology,Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing 100010,China

Department of Cardiology,Guang'anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China

Institute of Traditional Chinese Medicine Information,China Academy of Chinese Medical Sciences,Beijing 100700,China

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基金：

Special Scientific Research Project of the Chinese Medicine Industry of the State Administration of Traditional Chinese MediNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaFundamental Research Funds for the Central Public Welfare Research InstitutesFundamental Research Funds for the Central Public Welfare Research Institutes

项目编号：

201307006821046568200417982074405ZZ14-YQ-013ZZ15-YQ-024

出版年：

2024

DOI：

10.1007/s11655-024-3803-8

中国结合医学杂志(英文版)

中国中西医结合学会中国中医研究院

中国结合医学杂志(英文版)

CSTPCD

影响因子：1.056

ISSN：1672-0415

年,卷(期)：2024.30(9)