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Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
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Apoptosis signaling molecules as treatment targets in head and neck squamous cell carcinoma

Thomas J Ow1,2, Carlos Thomas2, Cory D Fulcher1

  • 1Department of Otorhinolaryngology-Head and Neck Surgery, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York, U.S.A.

The Laryngoscope
|January 3, 2020
PubMed
Abstract

Insights

Head and neck squamous cell carcinoma (HNSCC) cells resist apoptosis through BCL-xL and MCL-1. Therapeutic agents like navitoclax and bortezomib can induce apoptosis in HNSCC, offering a potential treatment strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Head and neck squamous cell carcinoma (HNSCC) exhibits complex signaling pathways that influence treatment resistance.
  • The BCL-2 family of proteins plays a critical role in regulating apoptosis, a key process in cancer cell death.

Purpose of the Study:

  • To investigate the expression of key BCL-2 family signaling molecules in HNSCC.
  • To assess the efficacy of therapeutic agents in inducing apoptosis in HNSCC cells.

Main Methods:

  • Messenger ribonucleic acid (mRNA) and protein expression of BAK, BAX, BCL-2, BCL2L1, and MCL1 were analyzed in HNSCC datasets and cell lines.
  • Cell viability and Annexin V assays were employed to evaluate the apoptotic effects of ABT-263 (navitoclax), A-1210477, and bortezomib.

Main Results:

  • BAK, BAX, BCL2L1, and MCL1 showed significantly higher expression than BCL2 in both The Cancer Genome Atlas (TCGA) and Montefiore Medical Center (MMC) datasets.
  • Protein expression patterns corroborated mRNA findings in HNSCC cell lines.
  • Treatment with combined ABT-263/A-1210477 or bortezomib induced apoptosis comparable to or exceeding the staurosporine control.

Conclusions:

  • HNSCC cells depend on BCL-xL and MCL-1 overexpression to inhibit apoptosis.
  • Targeting these anti-apoptotic signals with specific agents presents a viable therapeutic strategy for HNSCC.
Keywords:
A-1210477ABT-263Head and neck squamous carcinomaapoptosisbortezomib

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