Mechanism associated to enhancing the sensitivity of myeloma cells U266 to bortezomib by 2-methoxyestradiol.
- Author:
Shun-Quan WU
1
;
Zhen-Zhen XU
;
Hao-Bo HUANG
;
Jun LIN
;
Rong ZHAN
Author Information
1. Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
drug effects;
Boronic Acids;
pharmacology;
Bortezomib;
Cell Line, Tumor;
drug effects;
Cell Proliferation;
drug effects;
Drug Synergism;
Estradiol;
analogs & derivatives;
pharmacology;
Humans;
Pyrazines;
pharmacology
- From:
Journal of Experimental Hematology
2011;19(6):1424-1428
- CountryChina
- Language:Chinese
-
Abstract:
This study was aimed to explore the synergistic effect of 2-methoxyestradiol (2-ME2) and bortezomib (Bor) on the proliferative inhibition and apoptosis of U266 cell line and its possible mechanism. The cells were treated with 2-ME2, Bor alone and 2-ME2 combined with Bor, respectively. The cell viability and proliferative curve were detected by CCK8, the cell apoptosis was detected by caspase 3/7 activity test, cell cycle status was analyzed by flow cytometry, and real-time PCR was used to detect the mRNA expression of P21, BAX and BCL-2. The results showed that compared with cells treated with 2-ME2 or Bor alone, the proliferative potential of cells in combination group was significantly inhibited (p < 0.05), and apoptosis rate markedly increased (p < 0.05), cell cycle was arrested at G(1)-S phase, the mRNA expressive level of P21 and BAX increased, while the expression of BCL-2 decreased. It is concluded that 2-ME2 combined with Bor synergistically inhibits cell proliferation and induces apoptosis in U266 cell line. The possible mechanism may be associated with its effect of up-regulating P21 and BAX expressions.
