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

Kei Yamashiro, Kazutaka Nakao, Shigeo Ohba, Yuichi Hirose

研究成果: Article


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.

ジャーナルAnticancer research
出版物ステータスPublished - 01-01-2020


All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research