In vivo enhancement of chemosensitivity of human salivary gland cancer cells by overexpression of TGF-beta stimulated clone-22.

We have isolated transforming growth factor-beta-stimulated clone-22 (TSC-22) cDNA as an anti-cancer drug-inducible gene in a human salivary gland cancer cell line, TYS. We have previously reported that TSC-22 negatively regulates the growth of TYS cells, and that overexpression of TSC-22 protein in TYS cells enhanced the in vitro chemosensitivity of the cells. In this study, we examined the in vivo chemosensitivity of TSC-22-expressing TYS cells. TSC-22-expressing TYS cells formed tumors in nude mice, but tumors formed by TSC-22-expressing TYS cells were significantly smaller than tumors formed by control cells (p<0.001, one way ANOVA). Furthermore, intraperitoneal injection of 5-fluorouracil (5-FU) markedly inhibited the growth of the TSC-22-expressing TYS tumors, but did not affect the growth of control tumors. It was found by TUNEL assay that TSC-22-expressing TYS tumors were induced to undergo apoptosis by 5-FU treatment. These findings suggest that overexpression of TSC-22 protein in TYS cells enhances the in vivo chemosensitivity of the cells to 5-FU via induction of apoptosis.