HDAC inhibitor apicidin suppresses murine oral squamous cell carcinoma cell growth in vitro and in vivo via inhibiting HDAC8 expression

摘要

Apicidin, a cyclic peptide histone deacetylase (HDAC) inhibitor, has been demonstrated to exhibit antitumor activity in a number of human cancer types. The present study examined the antitumor activity of apicidin in murine oral squamous cell carcinoma (OSCC) cells. Inhibition of cell proliferation and the expression of selective HDACs were determined in apicidin-treated AT-84 murine OSCC cells. A C3H mouse model with subcutaneous injection of AT-84 cells was used to assess the in vivo effect of apicidin on tumor growth. Apicidin-induced cell growth inhibition and selectively reduced HDAC8 expression in AT-84 cells. Induction of apoptosis and autophagy was observed in apicidin-treated AT-84 cells. Apicidin notably inhibited tumor growth by up to 46% relative to the control group at the end of a 14-day period in a murine tumor model. The immunohistochemistry results in tumor tissues indicated that apicidin inhibited cell proliferation and induced apoptosis and autophagy in AT-84 cell-derived tumor tissues. Overexpression of HDAC8 was observed in the nucleus and cytoplasm in tumor tissues and apicidin significantly inhibited the level of HDAC8 expression, compared with the vehicle group. These results indicated that apicidin inhibited cell proliferation through HDAC8 inhibition in murine OSCC cells in vitro and in vivo. The present study indicated that apicidin may be an effective therapeutic agent for OSCC.