Human glioma cells acquire temozolomide resistance after repeated drug exposure via DNA mismatch repair dysfunction

研究成果: Article査読

2 被引用数 (Scopus)

抄録

Background/Aim: Temozolomide (TMZ) induces prolonged arrest of human glioma cells in the G2/M phase and inhibition of the G2 checkpoint intensifies the effect of TMZ. These findings suggest that the G2 checkpoint is linked to DNA repair mechanisms. Materials and Methods: To clarify the mechanism of TMZ resistance, we established TMZ-resistant (TR) clones by serial treatment of U87MG cells with TMZ. We evaluated TMZ-induced cell cycle arrest and the effect of various G2 checkpoint inhibitors. Results: We observed that longer exposure (over 6 months) to TMZ enriched the proportion of TR clones that underwent only minimal G2 arrest following TMZ treatment compared to short exposure (4 months) to TMZ. Expression of MSH6 was reduced in these clones. None of the G2 checkpoint inhibitors could resensitize TR clones to TMZ. Conclusion: Longer drug treatment may induce resistance of cells to DNA damaging agent(s) by means of mismatch repair modification.

本文言語English
ページ(範囲)1315-1323
ページ数9
ジャーナルAnticancer research
40
3
DOI
出版ステータスPublished - 2020

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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