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Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics
Published on: May 11, 2016
Establishment and characterization of triple drug resistant head and neck squamous cell carcinoma cell lines
Sindhu Valiyaveedan Govindan1, Safeena Kulsum1, Ramanan Somasundara Pandian2
1Integrated Head and Neck Oncology Research Program, DSRG‑5, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Foundation, Narayana Health, Bangalore, Karnataka 560099, India.
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.
Insights
Researchers developed triple drug-resistant head and neck cancer cell lines (TPFR) to study chemoresistance mechanisms. These models aid in understanding drug resistance and designing new cancer therapies.
Area of Science:
- Oncology
- Cancer Biology
- Pharmacology
Background:
- Chemotherapy resistance significantly impacts cancer patient outcomes, particularly in head and neck cancer.
- Effective treatment strategies for head and neck cancers often involve chemotherapy, but response rates vary.
- In vitro chemoresistant cell line models are crucial for investigating drug resistance mechanisms and developing new therapeutic agents.
Purpose of the Study:
- To generate head and neck cancer cell lines resistant to a triple chemotherapy regimen (docetaxel, cisplatin, and 5-fluorouracil).
- To establish valuable in vitro models for elucidating the mechanisms of chemoresistance.
- To provide a resource for the development of novel anti-cancer drugs and treatment strategies.
Main Methods:
- Two head and neck squamous cell carcinoma cell lines (Hep-2 and CAL-27) were used.
- Sequential exposure to increasing concentrations of docetaxel, cisplatin, and 5-fluorouracil (TPF) was employed to induce triple drug resistance.
- Generated resistant cell lines were designated Hep-2 TPFR and CAL-27 TPFR.
- Analyses included cell viability, apoptosis, cell cycle progression, and expression of multidrug resistance genes.
Main Results:
- Successfully generated triple drug-resistant head and neck cancer cell lines (Hep-2 TPFR and CAL-27 TPFR).
- Characterization of these resistant cell lines revealed alterations in cell viability, apoptosis, cell cycle, and multidrug resistance gene expression compared to parental cells.
- The study provides a foundation for further mechanistic studies into chemoresistance.
Conclusions:
- The developed TPFR cell lines serve as a valuable tool for studying chemoresistance in head and neck cancer.
- These models can facilitate the discovery of novel therapeutic targets and drug design for overcoming drug resistance.
- Further research using these models is warranted to improve treatment outcomes for head and neck cancer patients.
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