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Targeting mTOR-CCL20 Signaling May Improve Response to Docetaxel in Head and Neck Squamous Cell Carcinoma

Ming-Huei Chou1,2,3, Hui-Ching Chuang3,4, Yu-Tsai Lin3,4

  • 1Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.

International Journal of Molecular Sciences
|April 3, 2021
PubMed

Insights

New research shows docetaxel and mTOR inhibitors synergize to treat advanced head and neck squamous cell carcinoma (HNSCC). This combination therapy significantly inhibits cancer cell proliferation and migration, offering a promising new strategy for HNSCC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Advanced head and neck squamous cell carcinoma (HNSCC) presents a poor prognosis, necessitating novel therapeutic approaches.
  • The mammalian target of rapamycin (mTOR) pathway is frequently activated in HNSCC carcinogenesis, making it a key target for investigation.
  • Molecular targeted therapies offer potential as alternative or combination treatments for HNSCC.

Purpose of the Study:

  • To evaluate the efficacy of docetaxel and mTOR inhibitors as a combination therapy for HNSCC.
  • To investigate the role of the PI3K/mTOR/CCL-20 signaling pathway in HNSCC proliferation and migration.
  • To assess the synergistic effects of combining docetaxel with mTOR inhibitors (rapamycin, BEZ235) in HNSCC cell lines.

Main Methods:

  • Utilized human HNSCC cell lines (FaDu, SAS) and an orthotopic xenograft model.
  • Assessed cell proliferation and migration using WST-1 and Oris™ assays.
  • Examined PI3K/mTOR pathway activation via Western blot and immunohistochemistry.

Main Results:

  • Docetaxel significantly suppressed HNSCC cell proliferation and migration in vitro, mediated by the PI3K/mTOR/CCL-20 pathway.
  • mTOR inhibitors demonstrated dose-dependent inhibition of HNSCC cell growth and migration.
  • Combination therapy of mTOR inhibitors with docetaxel exhibited synergistic effects, leading to significant cell growth and migration arrest.

Conclusions:

  • Docetaxel effectively inhibits HNSCC cell proliferation and migration through the PI3K/mTOR/CCL-20 signaling pathway.
  • The combination of mTOR inhibitors and docetaxel shows significant synergistic and additive activity.
  • This combination therapy represents a promising new treatment strategy for advanced HNSCC.
Keywords:
BEZ235docetaxelhead and neck squamous cell carcinomamTOR-CCL-20rapamycin

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