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Anti-tumor activity and molecular mechanism of C3C12PPD in lung cancer / 中国药理学与毒理学杂志
Chinese Journal of Pharmacology and Toxicology ; (6): 286-287, 2018.
Article in Chinese | WPRIM | ID: wpr-705304
ABSTRACT
OBJECTIVE The aim of the present study was to investigate the anti-tumor effect and mechanism of a novel compound, C3C12PPD, a bioactive unnatural ginsenoside by metabolically engi-neered yeasts based on a new UDP-glycosyl- transferase from Bacillus subtilis. METHODS MTT assay was used to analyze the anti-proliferation activity of C3C12PPD in vitro. The effect of anti-tumor activity was observed by mouse Lewis xenograft model in vivo.The effects of C3C12PPD on suppressing the angio-genesis and invasion of A549 cells were investigated in vitro using Transwell and tube formation assays. RNAseq was used to find tagets of C3C12PPD. Western blotting was performed to investigate the expres-sion level of proteins in tumor tissues treated with C3C12PPD. RESULTS C3C12PPD could inhibit the growth of lung cancer in vitro and in viv o. At the dosage of 10.0 mg·kg-1, C3C12PPD inhibited tumor growth by 40.0% (P<0.05) in tumor weight in mouse Lewis xenograft. The inhibition of tube formation was 77.5%(P<0.01)and 80.3%(P<0.01)following treatment with 1×10-4and 2×10-4mol·L-1C3C12PPD for 5 h, whereas the proliferation of EA.hy926 cells was not influenced under the above concentrations. Under the concentrations of 1×10-4mol·L-1,C3C12PPD inhibited invasive ability of A549 cells(P<0.05).The results of RNAseq susgested that antitumor activity of C3C12PPD were associated with epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, the proteins related to EMT, Raf/MEK/ERK and AKT/mTOR signal pathways were effected by C3C12PPD analysed by western blotting. CONCLUSION These data suggested that C3C12PPD was able to supress lung cancer through inhibit EMT, invision and angiogenesis.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Pharmacology and Toxicology Year: 2018 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Pharmacology and Toxicology Year: 2018 Type: Article