Different treatment response in several head and neck squamous cell carcinoma cell lines possibly reflecting underlying molecular signatures

Abstract

Background: The treatment of HNSCC in Taiwan is still very challenging and might be related to betel-nuts use. Betel nut chewing might contribute to (1) strong inflammation, angiogenesis, and invasion; (2) easy recurrence or metastasis, usually accompanied with hypercalcemia; (3) not so good response to chemotherapy and epidermal growth factor receptor inhibitors; (4) relatively good response to vascular endothelial growth factor inhibitors combined with chemotherapy; (5) difficult wound healing. TCGA has divided HNSCC to 5 different subtypes by molecular signatures; betel-nuts related HNSCC in Taiwan might belong to the worst prognosis. Methods: We try to prove the difference of betel-nuts related cell lines in several aspects reflecting clinical characteristics of HNSCC in Taiwan. Other HNSCC cell lines will also be evaluated for their special characteristics. SCC4, SCC9, SCC15, SCC25, FaDu, KB, Cal27, SAS, and TW2.6(betel-nuts related) were used to evaluate (1) the in vitro drug sensitivity; (2) synergistic effect of some target therapies and irradiation with MTT assay, colony formation, flow cytometry, and western blotting. TW2.6 had already been proved to possess defective p53, p16 loss, and increased Bcl2. Results: Conclusions: TW2.6 might reflect treatment refractoriness of betel-nuts related HNSCC in Taiwan and be similar to EMT subtype (without HPV) in TCGA. In addition to PI3K/mTOR dual inhibition, AKT inhibitor, polo-like kinase inhibitor with radiation, CDK4/6 inhibitor, ALK/IGF-1R inhibitor, BCL2 inhibitor, & eribulin, Astragalus polysaccharides, FGFR inhibitor, & VEGFR2/PDGFR/FGFR or VEGFR2/c-MET/Axl triple blockage might be effective on TW2.6 and reverse treatment refractoriness, maybe through the inhibition of mesenchymal transformation & PI3K/AKT/mTOR signaling and the modulation of stemness, p-RB, & PD1/PDL1 pathway. Other HNSCC cell lines, according to their treatment response and molecular signatures, might also be correlated to other TCGA subtypes. Further NGS analysis may translate these HNSCC cell lines to represent TCGA subtypes to test efficacy for future novel therapies.