Tyrosine Kinase Inhibitors and Everolimus Reduce IGF1R Expression in HPV16-positive and -negative Squamous Cell Carcinoma

Anticancer Res. 2020 Jul;40(7):3847-3855. doi: 10.21873/anticanres.14374.

Abstract

Background/aim: The effects of tyrosine kinase inhibitors (TKI) in head and neck squamous cell cancer (HNSCC) are not fully understood. We investigated the effects of selective TKIs erlotinib, gefitinib, nilotinib, and dasatinib and the mTOR-inhibitor everolimus on the expression of insulin-like growth factor 1 receptor (IGF1R) in HPV-positive and HPV-negative squamous cancer cell lines.

Materials and methods: HPV-negative UMSCC-11A and UMSCC-14C cells and HPV-positive CERV196 cells were treated with TKIs or everolimus. Protein concentration of IGF1R was measured using ELISA.

Results: IGF1R expression was significantly reduced by all tested TKIs and everolimus in both HPV-negative cancer cell lines. In HPV-positive squamous cancer cells we observed significant protein inhibition.

Conclusion: The crosstalk between epidermal growth factor receptors and IGF1R could be of central interest for the development of novel medical approaches for individualized therapy.

Keywords: IGF1R; TKI; dasatinib; erlotinib; everolimus; gefitinib; head and neck squamous cell carcinoma (HNSCC); insulin-like growth factor 1 receptor; nilotinib.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Dasatinib / pharmacology
  • Erlotinib Hydrochloride / pharmacology
  • Everolimus / pharmacology*
  • Gefitinib / pharmacology
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / virology
  • Human papillomavirus 16 / isolation & purification*
  • Humans
  • Papillomavirus Infections / metabolism*
  • Papillomavirus Infections / virology
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrimidines / pharmacology
  • Receptor, IGF Type 1 / antagonists & inhibitors
  • Receptor, IGF Type 1 / biosynthesis*
  • Squamous Cell Carcinoma of Head and Neck / drug therapy*
  • Squamous Cell Carcinoma of Head and Neck / metabolism
  • Squamous Cell Carcinoma of Head and Neck / virology

Substances

  • Antineoplastic Agents
  • IGF1R protein, human
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Everolimus
  • Erlotinib Hydrochloride
  • Receptor, IGF Type 1
  • nilotinib
  • Dasatinib
  • Gefitinib