Chemotherapy of salivary gland carcinomas with tyrosine kinase inhibitors

化疗是治疗涎腺癌所必需的，因为这些肿瘤经常复发并转移到远处器官。如果肿瘤生长依赖于特定生长因子的信号，则中断这种信号将导致肿瘤的生长抑制。酸性成纤维细胞生长因子（aFGF）在小鼠下颌下腺中被证实，并被发现刺激小鼠下颌下腺未分化癌YT-12细胞的生长。此外，牛脑aFGF促进9，10-二甲基-1，2-苯并蒽诱导的颌下腺癌的发生。由于aFGF和FGF受体在正常下颌下腺和肿瘤中被证实，自分泌和旁分泌机制可能调节肿瘤的生长。Tyrphostins是一种人工合成的低分子量化合物，特异性抑制蛋白酪氨酸激酶。Tyrphostins抑制YT-12细胞的生长; Tyrphostin 9是最有效的抑制剂。此外，通过肿瘤内施用酪氨酸磷酸化抑制剂9抑制了由YT-12细胞接种诱导的裸鼠肿瘤的生长。它还抑制aFGF处理的YT-12细胞中包括FGF受体-1的膜蛋白的酪氨酸磷酸化。流式细胞仪分析、Hochest 33258 DNA染色和末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记法显示tyrpjostin 9诱导细胞周期阻滞和凋亡。这些结果表明，aFGF在小鼠颌下腺癌的发生发展中起作用，酪氨酸激酶抑制剂tyrphostin 9可作为颌下腺癌的抑制剂。

Chemotherapy is required for the treatment of salivary gland carcinomas, because these tumors recur and metastasize to distant organs frequently. If tumor growth were dependent on the signal of a specific growth factor, interruption of such signal would result in growth inhibition of the tumors. Acidic fibroblast growth factor (aFGF) was been demonstrated in the mouse submandibular gland and was found to stimulate the growth of mouse submandibular gland undifferentiated carcinoma YT-12 cells. Furthermore, bovine brain aFGF promoted the development of 9, 10-dimethyl-1, 2-benzanthracene-induced submandibular gland carcinomas. Since aFGF and FGF receptors were demonstrated in the normal submandibular glands and carcinomas, autocrine and paracrine mechanisms may regulate the growth of the tumors.Tyrphostins are artificial and low molecular weight compounds that specifically inhibit protein tyrosine kinases. Tyrphostins suppressed the growth of YT-12 cells ; tyrphostin 9 was the most potent inhibitor. Furthermore, the growth of nude mouse tumors induced by YT-12 cell inoculation was suppressed by intra-tumor administration of tyrphostin 9. It also inhibited tyrosine-phosphorylation of membrane proteins including FGF receptor-l in the aFGF-treated YT-12 cells. Flow cytometric analysis, DNA staining with Hochest 33258 and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method indicated that tyrpjostin 9 induced the arrest of cell cycle and apoptosis. These results suggest that aFGF play a role in the development of mouse submandibular gland carcinomas, and that tyrosine kinase inhibitor, tyrphostin 9, can be used as an inhibitor for the submandibular gland carcinoma.