Celecoxib in combination with retinoid CD437 inhibits melanoma A375 cell in vitro

Abstract

This study aimed to investigate the effects of celecoxib, synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic acid (CD437) and the combination of the two on cell proliferation, apoptosis, and cycle arrest of human malignant melanoma A375 cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-di-phenyltetrazoliumbromide assay (MTT assay) was applied to determine the anti-proliferative effects of the drugs on human malignant melanoma A375 cells. Flow cytometry was performed to investigate the influence of the drugs on cell cycle and cell apoptosis. Both celecoxib and CD437 could inhibit the growth of human malignant melanoma A375 cells in a dose-dependent manner. Celecoxib at 80 μmol/L inhibited proliferation, induced apoptosis and G₂/M cell cycle arrest of human malignant melanoma A375 cells after treatment for 24 h [proliferation inhibiting rate: (50.2±2.51)%, apoptosis rate: (35.91±1.80)%]. CD437 at 10 μmol/L inhibited proliferation, induced apoptosis and G₀/G₁ cell cycle arrest of human malignant melanoma A375 cells after treatment for 24 h [proliferation inhibiting rate: (58.6±2.38)%, apoptosis rate: (28.03±0.77)%]. Celecoxib in combination with CD437 could significantly enhance the effects of inhibiting proliferation and inducing apoptosis of human malignant melanoma A375 cells 24 h after treatment compared with the drug alone [proliferation inhibiting rate: (68.92±1.72)%, apoptosis rate: (42.09±1.05)%, both P<0.05] and could decrease the proportion of the S phase in the cell cycle. Celecoxib could inhibit the growth of human malignant melanoma A375 cells by inducing apoptosis and G₂/M cycle arrest. CD437 could inhibit the growth of human malignant melanoma A375 cells by inducing apoptosis and G₀/G₁ cycle arrest. Celecoxib exhibited additive effects with CD437 on retarding the growth and inducing apoptosis of human malignant melanoma A375 cells. Celecoxib in combination with CD437 may become an effective method for prevention and treatment of human melanoma.

Key words： celecoxib; CD437; melanoma A375 cell; apoptosis; cycle arrest

Acknowledgements

This study was supported by the National Natural Science Foundation of China (Grant No. 30371295).

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