ヒト口腔癌細胞株に対する酪酸ナトリウムの腫瘍増殖および浸潤抑制効果

抄録

Sodium butyrate, a histone deacetylase inhibitor, is well known to induce cell differentiation and to inhibit the proliferation of colorectal cancer cells and human glioma cells by inducing cell cycle arrest, differentiation, and apoptosis. However, there are few reports on the antitumor effects of sodium butyrate on human oral squamous cell carcinoma (OSCC) and anticancer-drug-resistant OSCC, and the mechanisms involved. In the present study, three OSCC cell lines (SAS, Ca9-22, and HSC-3), two cisplatin (CDDP)-resistant OSCC cell lines (SAS-SO and Ca9-22-TO), and a control cell line (normal gingival fibroblast Gin-1) were treated with various concentrations of sodium butyrate to evaluate inhibitory effects on cell proliferation and invasion. Cell proliferation was assayed using MT T, and invasion was assayed using Matrigel invasion chambers. The results demonstrated that sodium butyrate inhibited cancer cell proliferation and invasion by both OSCC cell lines and CDDP-resistant OSCC cell lines. In particular, when CDDP-resistant OSCC cell lines were pretreated with sodium butyrate before treatment with CDDP, the susceptibility of cancer cells to CDDP increased and a greater inhibitory effect on cancer cell proliferation was obtained at lower concentrations of CDDP. The mechanism by which sodium butyrate inhibits the proliferation of OSCC cell lines is suspected to involve suppression of cell cycle progression from G1 to S phase as indicated by BrdU-labeling index and flow cytometry, as well as by induction of apoptosis as shown by the appearance of DNA ladder.