Omotehara F, Uchida D, Hino S, Begum N M, Yoshida H, Sato M, Kawamata H
Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, Tokushima 770-8504, Japan.
Oncol Rep. 2000 Jul-Aug;7(4):737-40. doi: 10.3892/or.7.4.737.
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.
我们已从人唾液腺癌细胞系TYS中分离出转化生长因子-β刺激克隆-22（TSC-22）cDNA，作为一种抗癌药物诱导基因。我们之前报道过，TSC-22对TYS细胞的生长具有负调控作用，并且TSC-22蛋白在TYS细胞中的过表达增强了细胞的体外化学敏感性。在本研究中，我们检测了表达TSC-22的TYS细胞的体内化学敏感性。表达TSC-22的TYS细胞在裸鼠体内形成肿瘤，但表达TSC-22的TYS细胞形成的肿瘤明显小于对照细胞形成的肿瘤（p<0.001，单因素方差分析）。此外，腹腔注射5-氟尿嘧啶（5-FU）显著抑制了表达TSC-22的TYS肿瘤的生长，但不影响对照肿瘤的生长。通过TUNEL检测发现，5-FU处理可诱导表达TSC-22的TYS肿瘤发生凋亡。这些发现表明，TSC-22蛋白在TYS细胞中的过表达通过诱导凋亡增强了细胞对5-FU的体内化学敏感性。
