Resistance to chemotherapy leading to poor outcome and survival remains a challenge for developing strategies for therapeutic interventions in all types of cancer, including head and neck cancer. In vitro chemoresistant cell line models are an indispensable resource towards delineating
the mechanisms involved in drug resistance/response and for the development of novel drugs. Current treatment for head and neck cancer includes chemotherapy with cisplatin, docetaxel and 5fluorouracil (5FU) and the response rates to these drugs in patients is 6080%. The present study aimed
to generate head and neck cancer triple drugresistant cell lines in an effort towards elucidating the mechanisms underlying chemoresistance and providing a resourceful tool for drug design. Using two head and neck squamous cell carcinoma cell lines, Hep2 (larynx) and CAL27 (oral cavity), the
present study sequentially exposed these cells to increasing concentrations of the combination of docetaxel, cisplatin and 5FU (TPF) to generate triple drugresistant cells, termed Hep2 TPF resistant (TPFR) and CAL27 TPFR. The effect of the drug treatments on the cell viability, apoptosis,
cell cycle and the expression of genes associated with multidrug resistance were analyzed in the parental cells and drugresistant counterparts. The Hep2 TPFR and CAL27 TPFR cells exhibited a higher resistance index (RI≥2) compared with that of the parental cells. Cell cycle analysis
revealed a decreased number of TPFR cells in G0/G1 phase (P<0.05) and a corresponding accumulation of cells in G2/M phase. A reduced degree of apoptosis in these cells (Hep2, 33 vs 20%, P=0.003; and CAL27, 18 vs 9.7%) was complemented by an increased expression of genes involved in drug
resistance, including MDR1, MRP2, ERCC1, CTR, survivin and thymidylate synthase. The present study, therefore, established two multi drugresistant head and neck squamous cell carcinoma cell lines and characterized these cells on a cellular and molecular level. Development of these tools accentuates
their requirement in the field of drug discovery and in mechanistic studies elucidating the underlying mechanisms of drug resistance.
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Document Type: Research Article
Integrated Head and Neck Oncology Research Program, DSRG5, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Foundation, Narayana Health, Bangalore, Karnataka 560099, India
GROW Laboratory, Narayana Nethralaya, Narayana Health, Bangalore, Karnataka 560099, India
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo NY 14263, USA
Department of Head and Neck/Plastic and Reconstructive Surgery, Roswell Park Cancer Institute, Buffalo NY 14263, USA
Publication date: August 1, 2015
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Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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