Objective:

2

To investigate whether

Buthus martensii karsc

h (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:

2

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:

2

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:

2

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.