Selective cyclooxygenase-2 inhibitor celecoxib could sensitize B-cell-originated lymphoma cell lines ;to epirubicin via down-regulation of MDR-1 mRNA and Bcl-2 mRNA expression
10.3969/j.issn.1007-3969.2015.06.005
- VernacularTitle:选择性COX-2抑制剂塞来昔布抑制B细胞淋巴瘤细胞株MDR-1及Bcl-2的mRNA表达并增强表柔比星的抗肿瘤作用
- Author:
Fanli HUA
;
Lingyan WANG
;
Xin ZHAO
;
Ying LI
;
Yangjiong WU
;
Song GAO
- Publication Type:Journal Article
- Keywords:
Cyclooxygenase-2;
Celecoxib;
Lymphoma;
MDR-1 gene;
Bcl-2 gene
- From:
China Oncology
2015;(6):432-437
- CountryChina
- Language:Chinese
-
Abstract:
Background and purpose: It has been demonstrated that cyclooxygenase-2 (COX-2) is over-expressed in some subtypes of non-Hodgkin’s lymphoma (NHL), and COX-2 correlates with the expression of P-glycoprotein and Bcl-2, which may contribute to chemotherapy-resistance in NHL. The purpose of this study was to investigate the expression of COX-2 in B-cell lymphoma cell lines and the potential mechanisms of celecoxib, a selective COX-2 inhibitor, to sensitize lymphoma cell lines to epirubicin. Methods: Quantitative fluorescent real-time poly-chain-reaction (qRT-PCR) and Western blot were employed to determine the expression of COX-2 in Raji, Jeko-1 and Namalwa cell lines, as well as in peripheral blood B cells from normal controls. Cell lines were treated with celecoxib at gradient concentrations, followed by the detection of cell viabilities by cell counting kit-8 (CCK-8).Meanwhile, the changes in expression of MDR-1 mRNA and Bcl-2 mRNA before and after celecoxib treatment were determined by qRT-PCR. Raji cells were treated with epirubicin alone or in combination with gradient concentrations of celecoxib for 72 h, then CCK-8 was used to analyze whether celecoxib sensitize Raji cells to epirubicin. Results:Neither lymphoma cell lines nor normal B cells expressed detectable COX-2 in this study. Celecoxib inhibited the proliferation of the 3 lymphoma cell lines, and the mRNA expressions of MDR-1 and Bcl-2 were decreased by celecoxib in a concentration-dependent manner, except for that MDR-1 was undetectable in Jeko-1 cells. In addition, celecoxib sensitized Raji cells to epirubicin, indicating a synergistic anti-tumor effect between the two agents. Conclusion:Selective COX-2 inhibitor celecoxib down-regulates the expressions of MDR-1 mRNA and Bcl-2 mRNA in B-cell-originated lymphoma cell lines, and sensitizes Raji cells to epirubicin.
