大黄素对顺铂耐药卵巢癌细胞的逆转作用及其相关基因表达研究

天然产物研究与开发 ›› 2011, Vol. 23 ›› Issue (4): 638-642.

大黄素对顺铂耐药卵巢癌细胞的逆转作用及其相关基因表达研究

秦春明1，侯华新1*，程道海1，李力2，黎丹戎2，刘瑛1，宋慧1

1广西医科大学药学院，南宁 530021；2广西肿瘤防治研究所，南宁 530021

收稿日期:2010-10-25 出版日期:2011-08-25 发布日期:2011-09-13
基金资助:
国家自然科学基金资助项目(30660047)；广西自然科学基金资助项目(0728112)；广西研究生教育创新计划资助项目(2007105981007M09)

The Reversal Effect of Emodin on Cisplatin Resistance in Ovarian Cancer Cells and the Expression of Resistance-associated Genes

QIN Chun-ming1,HOU Hua-xin1,CHENG Dao-hai1,LI Li2,LI Dan-rong2,LIU Ying1,SONG Hui1

1College of Pharmacy Guangxi Medical University,Nanning 530021,China; 2Guangxi Cancer Institute,Nanning 530021,China

Received:2010-10-25 Online:2011-08-25 Published:2011-09-13

摘要/Abstract

摘要： 为了研究大黄素对人卵巢癌耐药细胞株SKOV3/DDP细胞耐药逆转作用及其机制，本研究以卵巢癌SKOV3和多药耐药细胞株SKOV3/DDP为研究对象，通过噻唑蓝(MTT)法测定SKOV3/DDP细胞的耐药指数和大黄素在无细胞毒浓度下对卵巢癌细胞耐受顺铂(DDP)的逆转作用；采用Real-time PCR技术检测耐药相关基因HIF-1α、STAT1、CK2α、GSTP1 mRNA表达情况。结果发现无细胞毒作用浓度的7.8 mg/L和3.9 mg/L大黄素能逆转SKOV3/DDP细胞对DDP的耐药性，对DDP的逆转倍数分别为1.91 倍和1.30 倍，与SKOV3比较，SKOV3/DDP细胞的HIF-1α、STAT1、CK2α、GSTP1 mRNA表达明显升高(P<0.01)。3.9 mg/L和7.8 mg/L 大黄素作用均可下调HIF-1α、CK2α、STAT1 mRNA表达，存在剂量-效应依赖关系。7.8 mg/L大黄素作用可下调GSTP1 mRNA表达，但3.9 mg/L 大黄素作用不明显。7.8 mg/L和3.9 mg/L 大黄素联合IC50浓度的DDP时，四个耐药相关基因的表达与单独化疗药组作用相比明显下调(P<0.01)。提示无细胞毒浓度的大黄素对卵巢癌细胞耐药逆转的作用可能是通过下调HIF-1α、STAT1、GSTP1、CK2α的表达起作用。

关键词: 大黄素；卵巢癌耐药细胞；耐药逆转；HIF-1&alpha, ；STAT1；GSTP1；CK2&alpha

Abstract: To inversitigate the drug resistance reversal effect and mechanism of emodin in cisplatinum-resistant ovarian cancer cells SKOV3/DDP (short for cisplatin) in vitro and study the expression of HIF-1α,STAT1,and GSTP1 resistance-associated genes.Methyl thiazolyl tetrazolium (MTT) method was used to detect the reversal index (RI) of SKOV3/DDP cells and the reversal effect of emodin.The resistance-associated genes expression of HIF-1α,CK2α,STAT1,and GSTP1 was detected by Real time PCR.The results showed that noncytotoxic dose of emodin reversed the cisplatin-resistance of SKOV-3/DDP,the reversal index (RI) was 1.91 and 1.30 respectively for 7.8 mg/L and 3.9 mg/L emodin.Compared with SKOV3 cells,expression level of HIF-1α,STAT1,CK2α,and GSTP1 mRNA in SKOV3/DDP was significantly raised(P<0.01).3.9 mg/L and 7.8 mg/L emodin could down regulated the gene expression of HIF-1α,CK2α,and STAT1 in a dose-dependent manner.Though 7.8 mg/L emodin down-regulated GSTP1 mRNA expression,3.9 mg/L emodin had no such effects.The mRNA expression level of those gene was significantly down-regulated when 7.8 mg/L and 3.9 mg/L emodin was combined with DDP (P<0.01).Emodin can down regulate the gene expression of HIF-1α,CK2α,STAT1,and GSTP1 on SKOV-3/DDP cells,which may account for the reversal effect of emodin on cisplatin resistance in ovarian cancer cells.

Key words: emodin, cisplatin-resistant ovarian cancer cells SKOV-3/DDP cell line, resistance reversal, HIF-1α, STAT1, GSTP1, CK2α

秦春明，侯华新，程道海，李力，黎丹戎，刘瑛，宋慧. 大黄素对顺铂耐药卵巢癌细胞的逆转作用及其相关基因表达研究[J]. 天然产物研究与开发, 2011, 23(4): 638-642.

QIN Chun-ming,HOU Hua-xin,CHENG Dao-hai,LI Li,LI Dan-rong,LIU Ying,SONG Hui. The Reversal Effect of Emodin on Cisplatin Resistance in Ovarian Cancer Cells and the Expression of Resistance-associated Genes[J]. NATURAL PRODUCT RESEARCH AND DEVELOPMENT, 2011, 23(4): 638-642.