Investigation On The Relationship Between Anti-proliferation Effect Of Honokiol On Human Colon Cancer SW620 Cells And BMP7/TGF-β1/p53 Signaling Pathway

Colorectal cancer(CRC)is the third most continually diagnosed cancer,which is a clinically conventional,highly malignant tumor of the digestive tract.Up to now,the underlying mechanisms remain abstruse,and there are some issues in drug treatment,such as deficient curative effect and toxicity.Therefore,to clarify the pathogenesis and explore the novel anti-tumor drugs for colon cancer treatment are urgently needed.Honokiol(HNK),a natural pharmaceutical ingredient extracted from magnolia bark,has been used in clinical treatment of various diseases,and has anti-inflammatory,anti-viral,and anti-oxidation functions.In the last few years,anti-cancer research has become a major hotpot.Previous studies have indicated that HNK may exert its anti-cancer function through BMP7/PI3K/Akt signaling pathway.The underlying other molecular mechanisms of HNK to inhibit colorectal cancer progression is to be clarified.The present study focused on elucidating the effects of HNK on the relationship between BMP7 and TGF-β signaling pathway in colon cancer.In this examination,we inquire into the anti-tumor activity of honokiol in colon cancer cells and explore its underlying anti-tumor mechanism using some basic molecular biological techniques.We found that HNK repressed the proliferation of colon cancer cells.Furthermore,HNK dramatically promoted the expression of BMP7 at both protein and m RNA levels,thereby enhancing the anti-cancer activity of HNK.Silencing of BMP7 contributed to opposite effects of HNK in SW620 cells.Moreover,further studies indicated that HNK could raise the expression of TGF-β1 and p53,which corresponded with overexpression of BMP7 in SW620 cells.In addition,immunohistochemical analysis also showed a positive correlation between BMP7 and TGF-β1 expression.The TGF-β1-selective inhibitor LY364947 could dramatically depress p53 and p-p53 expression,contrasted with HNK treatment alone.And LY364947 could attenuate the promotion effect of honokiol on p53 and p-p53 expression.The present results suggested that HNK is a promising anti-cancer agent for the treatment of colon cancer and enhanced the expression TGF-β1 and p53 through stimulating BMP7 activity via the non-canonical TGF-β signaling pathway.