OBJECTIVETo investigate the in vitro effect of bortezomib (BTZ) alone and in combination with pirarubicin (THP) on the growth inhibition of human cutaneous T-cell lymphoma cell line Hut-78.

METHODSHut-78 cells were cultured with different concentrations of BTZ or THP alone and the two drugs combination for 48 h. Cell proliferation, cell cycle and apoptosis were evaluated. The cell cycle inhibitor P21 was determined by Western blot.

RESULTSBTZ or THP alone significantly inhibited the growth of Hut-78 cells in a time- and dose-dependent manner. In the combination groups, the inhibitory effect of BTZ followed by THP was the highest (P < 0.01). When the inhibition rate was more than 50%, the combination index analysis showed significant synergistic if treated with BTZ followed by THP or the two at the same time, but antagonistic if treated with THP followed by BTZ. With the inhibition rate increasing, only the synergistic effect of BTZ followed by THP was further increased. The apoptosis rate of BTZ followed by THP was higher than that of single agent each (P < 0.01). BTZ alone significantly increased the proportion of cells in G(2)/M phase (P < 0.01) in a dose-dependent manner and up-regulated the expression level of P21. Sequential THP notably enhanced BTZ-induced cell cycle arrest and apoptosis.

CONCLUSIONSBTZ alone effectively induces growth inhibition and apoptosis of Hut-78 cells in vitro. BTZ followed by THP can synergistically enhance this cytotoxic effect. The mechanism may be that THP enhances BTZ-induced G(2)/M arrest and P21 up-regulation.