中国药理学通报2012，Vol.28Issue(8)：1101-1105,5.DOI:10.3969/j.issn.1001-1978.2012.08.015
胡椒碱与棉酚联用对前列腺癌DU145细胞生长抑制的协同作用
Synergistic inhibition of growth of prostate cancer DU145 cells by combined piperine and gossypol treatment
摘要
Abstract
Aim To investigate the effect of combined piperine and gossypol in inhibition of the growth of an-drogen-independent prostate cancer DU145 cells and e-lucidate the underlying mechanism. Methods MTS assay was adopted to measure the cell viability. Cell cycle distribution was analyzed by flow cytometry. Western blotting was used to determine the expression of cell cycle related proteins and CYP3A4. Results Piperine was relatively low toxic to DU145 cells, whereas when it was used in combination with gossypol, the IC50 of gossypol was decreased from 21. 00 μmol · L-1 to 8. 07 μmol · L-1 . The coefficient of drug interaction was less than 1, demonstrating that piperine plus gossypol had a synergistic effect on inhi- bition of the growth of DU145 cells. The combined drugs also significantly arrested cells at G0/G1 phase, and increased sub-G0/G1 peak (apoptotic peak). Moreover, the combined piperine and gossypol also results in an increased level of p21Cip1 expression and decreased expression levels of Cyclin D1, Cyclin A, Cyc-lin B1 and drug-metabolic enzyme CYP3A4. Conclusion The combination of piperine and gossypol results in synergistic inhibition of DU145 cell growth through induction of cell cycle arrest, increase of cell apoptosis and inhibition of CYP3A4 activity.关键词
胡椒碱/棉酚/前列腺癌细胞DU145/协同作用/细胞周期/CYP3A4Key words
piperine/ gossypol/ DU145 prostate cancer cells/synergistic effect/cell cycle/CYP3A4分类
医药卫生引用本文复制引用
曾龙辉,徐丽慧,何贤辉,欧阳东云,张延亭,任帅..胡椒碱与棉酚联用对前列腺癌DU145细胞生长抑制的协同作用[J].中国药理学通报,2012,28(8):1101-1105,5.基金项目
国家自然科学基金资助项目(No 81173604) （No 81173604）
十二五新药创制专题(No 2011ZX09307-303-03) （No 2011ZX09307-303-03）
