Su Yu-Chieh, Wang Chih-Chun, Weng Jui-Hsi, Yeh Shyh-An, Chen Po-Jen, Hwang Tzer-Zen, Chen Huang-Chi
School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan.
Division of Hematology-Oncology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan.
Front Oncol. 2022 Jul 22;12:834941. doi: 10.3389/fonc.2022.834941. eCollection 2022.
Head and neck squamous cell carcinoma (HNSCC) is a common cancer of the oral cavity. Cisplatin (CDDP) is the ideal chemo-radiotherapy used for several tumor types, but resistance to the drug has become a major obstacle in treating patients with HNSCC. 5-methoxytryptophan (5-MTP), a 5-methoxyindole metabolite of tryptophan metabolism, reduces inflammation-mediated proliferation and metastasis. This study aimed to assess the anti-oral cancer activity of 5-MTP when used alone or in combination with CDDP. Results showed that CDDP dose dependently reduced the growth of SSC25 cells but not 5-MTP. The combination of CDDP and 5-MTP exerted additional inhibitory effect on the growth of SSC25 cells by attenuating the phosphorylation of STAT3. In the 4-nitroquinoline-1-oxide-induced oral cancer mouse model, 5-MTP sensitized the reduction effect of CDDP on tumorigenesis, which restricted the tongue tissue in hyperkeratotic lesion rather than squamous cell carcinoma. The combination of CDDP and 5-MTP may be a potent therapeutic strategy for HNSCC patients with radiotherapy.
头颈部鳞状细胞癌（HNSCC）是口腔常见的癌症。顺铂（CDDP）是用于多种肿瘤类型的理想放化疗药物，但对该药物的耐药性已成为治疗HNSCC患者的主要障碍。5-甲氧基色氨酸（5-MTP）是色氨酸代谢的一种5-甲氧基吲哚代谢产物，可减少炎症介导的增殖和转移。本研究旨在评估5-MTP单独使用或与CDDP联合使用时的抗口腔癌活性。结果表明，CDDP剂量依赖性地降低了SSC25细胞的生长，但对5-MTP无此作用。CDDP与5-MTP联合使用通过减弱STAT3的磷酸化对SSC25细胞的生长产生额外的抑制作用。在4-硝基喹啉-1-氧化物诱导的口腔癌小鼠模型中，5-MTP增强了CDDP对肿瘤发生的抑制作用，其将舌组织限制在角化过度病变而非鳞状细胞癌中。CDDP与5-MTP联合使用可能是HNSCC放疗患者的一种有效治疗策略。
