关键词: 环氧合酶-2, 塞来昔布, 淋巴瘤, MDR-1基因, Bcl-2基因

Abstract:    Background and purpose: It has been demonstrated that cyclooxygenase-2 (COX-2) is overexpressed 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 realtime 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.

Key words: Cyclooxygenase-2, Celecoxib, Lymphoma, MDR-1 gene, Bcl-2 gene