Acta Pharmacologica Sinica 2006 November; 27 (11): 1447-1452; doi: 10.1111/j.1745-7254.2006.00343.x

Aim: To examine the in vitro antitumor activity of resveratrol against multiple myeloma (MM) cell lines (RPMI 8226, U266, and KM3), and the mechanisms involved.

Methods: The growth inhibition of resveratrol was determined by 3-(4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The effect of resveratrol on the apoptosis was investigated by combined annexin V-propidium iodide staining. The effect of resveratrol on the invasion through Matrigel matrix was detected by transwell invasion analyses. The activity of matrix metalloproteinase (MMP)-2 and -9 proteins were determined by gelatin zymography analysis. The expression of MMP-2, MMP-9, Bcl-2, Bcl-x_L, XIAP and Bax protein were detected using Western blotting analysis.

Results: Resveratrol inhibited proliferation of MM cells in a dose- and time-dependent manner. Incubation of MM cells with resveratrol resulted in apoptotic cell death. Resveratrol down-regulated the expression of the antiapoptotic proteins Bcl-2, Bcl-x_L and XIAP and up-regulated the expression of the proapoptotic protein Bax. Furthermore, resveratrol inhibited invasion of RPMI 8226, U266, and KM3 cells with IC₅₀ values of 64±8 µmol/L, 93±11 µmol/L, and 153±11 µmol/L, respectively. Resveratrol inhibited the constitutive expression of MMP-2 and -9 proteins of MM cells and suppressed its gelatinolytic activity.

Conclusion: Resveratrol inhibits the proliferation of MM cells by inducing apoptotic cell death. Resveratrol also inhibits MM cell invasion. The inhibition of invasion may be associated with the attenuation of the enzymatic activities of MMP-2 and -9.

Keywords: resveratrol; multiple myeloma; proliferation; invasion; matrix metalloproteinase

³ Correspondence to Prof Yu HU.
Phn 86-27-6276-6183.
Fax 86-27-8577-6343.
E-mail ayan0618@163.com
Received 2005-12-08     Accepted 2006-02-08