Frontiers in Oncology (Jul 2022)

5-Methoxytryptophan Sensitizing Head and Neck Squamous Carcinoma Cell to Cisplatitn Through Inhibiting Signal Transducer and Activator of Transcription 3 (STAT3)

  • Yu-Chieh Su,
  • Yu-Chieh Su,
  • Chih-Chun Wang,
  • Chih-Chun Wang,
  • Jui-Hsi Weng,
  • Shyh-An Yeh,
  • Shyh-An Yeh,
  • Po-Jen Chen,
  • Tzer-Zen Hwang,
  • Tzer-Zen Hwang,
  • Huang-Chi Chen,
  • Huang-Chi Chen

DOI
https://doi.org/10.3389/fonc.2022.834941
Journal volume & issue
Vol. 12

Abstract

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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.

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