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Scorpiones, Scolopendra and Gekko Inhibit Lung Cancer Growth and Metastasis by Ameliorating Hypoxic Tumor
Qi-Yuan Mao1, Xue-Qian Wang1, Fei Lin1
1Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China.
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<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-1α signaling pathway.
Insights
Traditional Chinese medicines Buthus martensii karsch (Scorpiones), Scolopendra subspinipes mutilans L. Koch (Scolopendra), and Gekko gecko (Gekko) show promise in treating lung cancer. These agents ameliorate the hypoxic tumor microenvironment and inhibit cancer growth by regulating the PI3K/AKT/mTOR/HIF-1α pathway.
Area of Science:
- Pharmacology and Toxicology
- Oncology
- Molecular Biology
Background:
- The tumor microenvironment, particularly hypoxia, plays a critical role in lung cancer progression and metastasis.
- The phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor-1α (PI3K/AKT/mTOR/HIF-1α) signaling pathway is frequently dysregulated in cancer, promoting tumor growth and survival.
- Traditional Chinese medicines are increasingly explored for their therapeutic potential in cancer treatment.
Purpose of the Study:
- To investigate the effects of Buthus martensii karsch (Scorpiones), Scolopendra subspinipes mutilans L. Koch (Scolopendra), and Gekko gecko (Gekko) on lung cancer.
- To determine if these agents can ameliorate the hypoxic tumor microenvironment and inhibit lung cancer growth and metastasis.
- To elucidate the role of the PI3K/AKT/mTOR/HIF-1α signaling pathway in the observed effects.
Main Methods:
- Lung cancer models were established in male C57BL/6J mice using LL/2-luc-M38 cells.
- Mice were treated with Scorpiones, Scolopendra, and Gekko extracts, with rapamycin and cyclophosphamide as positive controls.
- Tumor growth, metastasis, HIF-1α and CD31 expression, microvessel density (MVD), and key proteins and factors in the PI3K/AKT/mTOR/HIF-1α pathway (including bFGF, TGF-β1, VEGF) were analyzed.
Main Results:
- Scorpiones, Scolopendra, and Gekko significantly prolonged survival and inhibited lung cancer metastasis and HIF-1α expression.
- These agents suppressed the phosphorylation of AKT and p70S6K, key components of the PI3K/AKT/mTOR pathway.
- Treatment reduced CD31 expression, MVD, and levels of bFGF, TGF-β1, and VEGF, indicating reduced angiogenesis and altered tumor microenvironment.
Conclusions:
- Buthus martensii karsch (Scorpiones), Scolopendra subspinipes mutilans L. Koch (Scolopendra), and Gekko gecko (Gekko) demonstrate significant anti-lung cancer effects.
- These beneficial effects are mediated by the amelioration of the hypoxic tumor microenvironment through the regulation of the PI3K/AKT/mTOR/HIF-1α signaling pathway.
- The findings support the potential of these traditional medicines as complementary therapies for lung cancer.
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