Mechanism Prediction of Monotropein for the Treatment of Colorectal Cancer by Network Pharmacology Analysis

Objective To discover the pharmacological mechanisms of monotropein in colorectal cancer by network pharmacology methods.Methods The main-candidate-target network was constructed by the prediction of targets of monotropein, collection of therapeutic targets of colorectal cancer drugs, and construction of the target network and layers of screening. The data were interpreted by pathway enrichment and target score calculation.Results This study:(1) Demonstrated the potential of monotropein to be a multi-target drug against colorectal cancer using a computational approach;(2) Discovered 10 candidate targets of monotropein, among which protein kinase B(AKT1)exhibited the highest relevance and importance to colorectal cancer and proto-oncogene tyrosine-protein kinase Src(SRC),Bruton’s tyrosine kinase(BTK), and heat shock protein HSP 90-alpha(HSP90 AA1) also exhibited high relevance;(3) Observed 32 possible pathways related to the effects of monotropein on colorectal cancer, which might explain the mechanism of its action;and(4) Established a method to assess the importance of targets in the network.Conclusions This study offered clues for the mechanism of the bioactivities of monotropein against colorectal cancer by network analysis. Monotropein has the potential to be a multi-target drug against colorectal cancer, which lays the foundation for its clinical applications and further study.

OVEREXPRESSION OF Akt-1 GENE IN HUMAN HEPATOCELLULAR CARCINOMA

Objective: To investigate the expression difference of protein kinase B/Akt (Akt-1) between hepatocellular carcinoma (HCC) and adjacent normal liver tissues through the use of semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Northern blot. Methods: RT-PCR of 24 pairs of specimens and Northern blot of 4 pairs of specimens were performed to investigate the expression of Akt-1. Results: Akt-1 gene was overexpressed in 15 of 24 HCC (63.3%) by RT-PCR and in all HCC (4 paired tissues) by Northern blot. Conclusion: Akt-1 activation may play a role in the pathogenesis and progression of HCC. Akt-1 gene is reported to have changed in HCC for the first time. The precise relationship between Akt-1 and HCC is a matter of further investigation.

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

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.