Osthole enhances doxorubicin-induced apoptosis in p53-wildtype prostate cancer cells by down-regulating SIRT1 expression
10.3969/j.issn.1000-4718.2018.03.009
- VernacularTitle:蛇床子素通过抑制SIRT1的表达增强阿霉素对p53野生型前列腺癌细胞的凋亡诱导活性
- Author:
Xiao-Di CHEN
1
;
Xian-Bao ZHAO
;
Gao-Jian LUO
Author Information
1. 义乌市中心医院中医科
- Keywords:
Osthole;
Silent information regulator 1;
Doxorubicin;
Prostate cancer;
Apotosis
- From:
Chinese Journal of Pathophysiology
2018;34(3):435-440
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the effect and mechanism of osthole on increasing the cytotoxicity of doxorubi -cin(DOX)to prostate cancer cells.METHODS:MTT assay was performed to evaluate the viability of LNCaP cells trea-ted with osthole and DOX.The protein expression of silent information regulator 1(SIRT1),p53,acetylated p53 and Pu-ma,as well as release of cytochrome C and activation of caspase-9 and caspase-3 in the LNCaP cells treated with osthole and DOX were determined by Western blot.The apoptosis of the LNCaP cells treated with osthole and DOX was analyzed by flow cytometry.RESULTS:Osthole significantly increased the cytotoxicity of DOX against p 53-wildtype prostate cancer cell line LNCaP.Osthole significantly inhibited the expression of SIRT 1 in the LNCaP cells.Transfection with SIRT1 plas-mid decreased the cytotoxicity of osthole and DOX co-treatment against LNCaP cells.Combination with osthole and DOX significantly induced the over-expression and acetylation of p53.Transfection with p53 siRNA significantly decreased the synergistic effect of osthole on cytotoxicity of DOX-treated LNCaP cells.Combination with osthole and DOX significantly in-duced the release of cytochrome C into the cytoplasm from mitochondria,followed by activation of caspase-9 and its down-stream molecule caspase-3,thus leading to cell apoptosis in the LNCaP cells.CONCLUSION:Osthole promotes the p53-dependent apoptosis in DOX-treated prostate cancer LNCaP cells by down-regulating the expression of SIRT1.
