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首页> 中文期刊> 《亚太热带生物医学杂志：英文版》 >Achillea biebersteinii extracts suppress angiogenesis and enhance sensitivity to 5-fluorouracil of human colon cancer cells via the PTEN/AKT/mTOR pathway in vitro

Achillea biebersteinii extracts suppress angiogenesis and enhance sensitivity to 5-fluorouracil of human colon cancer cells via the PTEN/AKT/mTOR pathway in vitro

         
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Objective:To investigate the antiproliferative,anti-angiogenic,and apoptotic effects of extracts of Achillea biebersteinii(ABE)and combined treatments of ABE with 5-fluorouracil(5-FU)on HT-29 cells.Methods:The effects of ABE,5-FU,and combined treatments on the viability of HT-29 cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Isobologram analysis was used to determine synergism between ABE and 5-FU.The apoptotic and anti-angiogenic effects were determined by cell death detection and human vascular endothelial growth factor ELISA method,respectively.Transcriptional and translational expressions of p53,Bax,Bcl-2,p38 MAPK,Akt,PTEN,and m TOR were also evaluated by real-time PCR and Western blotting analysis.Results:ABE decreased the viability of HT-29 cells in a dosedependent manner.Combined treatment of hexane,chloroform,and methanol extracts of Achillea biebersteinii with 5-FU at IC50 doses decreased the cell viability to 26.0%,19.1%,and 14.9%,respectively(P<0.001).Furthermore,ABE treatment alone and combination with 5-FU,induced apoptosis,significantly downregulated m TOR,Akt,Bcl-2 expression,upregulated p53,Bax,PTEN,p38 MAPK expression,and exhibited anti-angiogenetic effects.Conclusions:Our findings indicate that ABE shows synergism with 5-FU and inhibits the proliferation of HT-29 cells by inducing apoptosis and suppressing angiogenesis,which may provide biological evidence for further use of ABE in the treatment of colorectal cancer.

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