Reversal of nomegestrol acetate on multidrug resistance in drug-resistant human breast cancer cell line MCF7/ADR

	Reversal of nomegestrol acetate on multidrug resistance in drug-resistant human breast cancer cell line MCF7/ADR
	Li Jie; Xu Liangzhong; He Kailing; Guo Weijian; Zhu Xiongzeng; Zheng Yunhong; Xia Peng
刊名	Chinese Journal of Oncology
	2002
卷号	24 期号:2 页码:129-132
关键词	nomegestrol acetate multidrug resistance MCF 7 cell
ISSN号	0253-3766
其他题名	诺美孕酮逆转乳腺癌耐药细胞株多药耐药性的研究
文献子类	Article
英文摘要	Objective To study the reversal effect of nomegestrol acetate (NOM) on mutidrug resistance (MDR) in MCF7/ADR and its mechanism. Methods Using tetrazolium dye assay, effects of various concentrations of NOM on sensitivity to ADR in MCF7/ADR was studied. Expression of MDR related genes MDR1, glutathoine S-transferase Pi (GST7r), Topoisomerase II a (TopoH a) and MDR related protein (MRP) were assayed by reverae transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry assay. Using flow cytometry ( FCM), intracellular ADR concentration effects on cell cycle were observed. Results NOM significantly reversed MDR in MCF7/ADR. After NOM 20, 10 and 5 jumol/L treatment, the chemosensitivity to ADR increased to 21, 12 and 8 times. The reversal activity of NOM was stronger than that of the precursor compound megestrol acetate, and was comparable to that of verapamail. After treatment with NOM 5 fimol/L both MDR1 and GSTtt mRNA genes expression began to decline on D2 ( P < 0. 05, & P < 0. 01) and reached the lowest level on D3 (both P < 0.01), but the expression levels began to rise on D6 again (both P < 0.05). The expression of MRP and Topo H a gave no significant change. Changes of P-gp and GSTw protein expressions were similar to those of their mRNA expressions, showing'early decline and late rise. Two hours after NOM 20, 10, and 5 jiunol/L treatment, intracellular ADR concentration increased 2.7, 2.3 and 1.5 limes, respectively. FCM data showed thai after forty-eight horn's, combined administration of NOM (20 jumol/L) and ADR (from low concentration to high concentration), MCF7/ADR cells showed gradual arrest in the G2M phase with the increase of ADR dose. Conclusion NOM has strong reversal effects on MDR in MCF7/ADR. The reversal takes place via different routes, i. e. down regulating mRNA and protein expression levels of MDR1 and GSTit, increasing intracellular drug concentration, and enhancing the arrest of ADR in cells at G^M phase.
WOS研究方向	Oncology (provided by Clarivate Analytics)
语种	中文
CSCD记录号	CSCD:1106670
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/268475]
专题	中国科学院上海药物研究所
作者单位	Department of Oncology, Xin Hua Hospital Cancer Center, Shanghai Second Medical University, Shanghai 200092, China.
推荐引用方式 GB/T 7714	Li Jie,Xu Liangzhong,He Kailing,et al. Reversal of nomegestrol acetate on multidrug resistance in drug-resistant human breast cancer cell line MCF7/ADR[J]. Chinese Journal of Oncology,2002,24(2):129-132.
APA	Li Jie.,Xu Liangzhong.,He Kailing.,Guo Weijian.,Zhu Xiongzeng.,...&Xia Peng.(2002).Reversal of nomegestrol acetate on multidrug resistance in drug-resistant human breast cancer cell line MCF7/ADR.Chinese Journal of Oncology,24(2),129-132.
MLA	Li Jie,et al."Reversal of nomegestrol acetate on multidrug resistance in drug-resistant human breast cancer cell line MCF7/ADR".Chinese Journal of Oncology 24.2(2002):129-132.