Methotrexate-induced senescence in human adenocarcinoma cells is accompanied by induction of p21(waf1/cip1) expression and lack of polyploidy

作者：Dabrowska Magdalena^*; Mosieniak Grazyna; Skierski Janusz; Sikora Ewa; Rode Wojciech

来源：Cancer Letters, 2009, 284(1): 95-101.

DOI：10.1016/j.canlet.2009.04.015

• High dose methotrexate
• Colorectal adenocarcinoma
• Growth arrest
• Accelerated senescence
• Multinucleation

Human colorectal adenocarcinoma C85 cells, treated with high dose methotrexate (1 mu M; IC50 = 51 nM), undergo accelerated senescence, as the cells (i) are growth arrested at the G(1) and S phases of the cell cycle, (ii) are SA-beta-galactosidase-positive, (iii) show induced expression of p21(waf1/cip1) and decreased expression of p16(INK4a), and (iv) show DNA synthesis continued at the reduced level. The fraction of C85 cells with DNA content higher than 4 N is maintained at the same level (14%) in cells untreated, as well as regrown after the treatment. Multinucleation is found as the main karyotypic abnormality.

• 出版日期2009-10-18