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Cell-cycle distribution and Thymidilate Synthatase (TS) expression correlate with 5-FU resistance in head and neck

Kei Ijichi1, Makoto Adachi2, Tetsuya Ogawa3

  • 1Department of Otolaryngology-Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan ijichi@med.nagoya-cu.ac.jp.

Anticancer Research
|June 13, 2014
PubMed
Abstract

Insights

Acquired resistance to 5-fluorouracil (5-FU) chemotherapy in head and neck cancer involves increased Thymidylate Synthase (TS) expression and cell-cycle changes. These mechanisms offer insights into overcoming 5-FU chemoresistance.

Area of Science:

  • Oncology
  • Cancer Chemotherapy
  • Molecular Biology

Background:

  • Acquired chemoresistance to 5-fluorouracil (5-FU) is a significant challenge in cancer treatment.
  • The precise molecular mechanisms underlying acquired 5-FU resistance are not fully understood.
  • 5-FU primarily functions by inhibiting Thymidylate Synthase (TS), a key enzyme in DNA replication.

Purpose of the Study:

  • To investigate the mechanisms of acquired 5-FU resistance in head and neck squamous cell carcinoma.
  • To compare the cellular responses of parental and 5-FU-resistant cell lines to 5-FU treatment.

Main Methods:

  • Utilized head and neck squamous cell carcinoma cell lines (UM-SCC-23) and derived 5-FU-resistant variants (UM-SCC-23/WR, UM-SCC-23/MR).
  • Analyzed differences in cell-cycle distribution and Thymidylate Synthase (TS) protein expression.
  • Employed flow cytometric analysis to compare cell-cycle profiles of resistant and parental cells post-5-FU treatment.

Main Results:

  • UM-SCC-23/WR cells exhibited a significant increase in TS protein expression after 5-FU treatment.
  • Both parental (UM-SCC-23) and resistant (UM-SCC-23/WR) cells showed an immediate increase in S-phase following 5-FU exposure.
  • The UM-SCC-23/MR resistant cell line displayed a delayed accumulation in S-phase after 5-FU treatment.

Conclusions:

  • Cell-cycle perturbation and elevated TS protein expression are implicated in acquired 5-FU resistance.
  • These findings elucidate specific 5-FU resistance mechanisms related to different treatment regimens.
Keywords:
5-FUcell cyclehead and neck carcinomaresistancethymidylate synthase

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