Antitumor efficacy of combination of celecoxib and rapamycin in MDA-MB-231 human breast cancer cells

2008 
Objective To explore the antitumor efficacy of combination of eelecoxib and rapamyein in MDA-MB-231 human breast cancer cells. Methods The effects of different coneentratians of celecoxib (20,40,60 and 80 μmol/L) alone, rapamycin ( 1,10, 100,1000 nmol/L) alone, or 60 μmol/L celecoxib in combination with 100 nmol/L rapamycin on cell growth were detected by using MTT. The cell cycle and apoptosis were analyzed by flow eytometry. The expression of HER2 and HER3 and level of phosphorylation of hkt (473) were also detected by using method of Western blot. Results Celeeoxib alone or rapamyein alone markedly inhibited MDA-MB-231 cell growth at a dose- and time-dependent manner. Compared with 60 μmol/L celecoxib or 100 nmol/L rapamycin alone treatment ,60 μmol/L celecoxib in combination with 100 nmol/L rapamycin produced synergistic inhibitory effects on cell growth and apoptosis [ (88.0±8.0)% vs (52.0 ±5.0)% or (54.0 ±6.0)%,(32.5 ±3.0)% vs (12.6 ±2.0)% or (7.2 ± 2. O) % ] ( P < 0. O1 ). The enhanced antitumor effect of the combined agents was associated with the decreased expression of HER2, HER3 and level of phosphorylation of Akt (473) in MDA-MB-231 ceils. Conclusion Enhanced anti-cancer effect is achieved in MDA-MB-231 human breast cancer ceils by combining celecoxib and rapamyein. The combination of celecoxib and rapamyein may increase the clinical potential benefits of these agents to sub-populations of HER2 and HER3-positive breast cancer. Key words: Celecoxib;  Rapamyein;  Breast carcinoma
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