title: Establishment and characterization of triple drug resistant head and neck squamous cell carcinoma cell lines.
abstract: 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 5-fluorouracil (5-FU) and the response rates to these drugs in patients is 60-80%. The present study aimed to generate head and neck cancer triple drug-resistant 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, Hep-2 (larynx) and CAL-27 (oral cavity), the present study sequentially exposed these cells to increasing concentrations of the combination of docetaxel, cisplatin and 5-FU (TPF) to generate triple drug-resistant cells, termed Hep-2 TPF resistant (TPFR) and CAL-27 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 drug-resistant counterparts.
authors.affiliation: Integrated Head and Neck Oncology Research Program, DSRG‑5, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Foundation, Narayana Health, Bangalore, Karnataka 560099, India.
authors.forename: Sindhu Valiyaveedan
authors.initials: SV
authors.lastname: Govindan
authors.affiliation: Integrated Head and Neck Oncology Research Program, DSRG‑5, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Foundation, Narayana Health, Bangalore, Karnataka 560099, India.
authors.forename: Safeena
authors.initials: S
authors.lastname: Kulsum
authors.affiliation: GROW Laboratory, Narayana Nethralaya, Narayana Health, Bangalore, Karnataka 560099, India.
authors.forename: Ramanan Somasundara
authors.initials: RS
authors.lastname: Pandian
authors.affiliation: GROW Laboratory, Narayana Nethralaya, Narayana Health, Bangalore, Karnataka 560099, India.
authors.forename: Debashish
authors.initials: D
authors.lastname: Das
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo NY 14263, USA.
authors.forename: Mukund
authors.initials: M
authors.lastname: Seshadri
authors.affiliation: Department of Head and Neck/Plastic and Reconstructive Surgery, Roswell Park Cancer Institute, Buffalo NY 14263, USA.
authors.forename: Wesley
authors.initials: W
authors.lastname: Hicks
authors.affiliation: Integrated Head and Neck Oncology Research Program, DSRG‑5, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Foundation, Narayana Health, Bangalore, Karnataka 560099, India.
authors.forename: Moni Abraham
authors.initials: MA
authors.lastname: Kuriakose
authors.affiliation: Integrated Head and Neck Oncology Research Program, DSRG‑5, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Foundation, Narayana Health, Bangalore, Karnataka 560099, India.
authors.forename: Amritha
authors.initials: A
authors.lastname: Suresh
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology* / Q000633:toxicity; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D002945:Cisplatin; D000077143:Docetaxel; D005472:Fluorouracil; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; D043823:Taxoids