Your browser doesn't support javascript.
loading
Reversal effects of desipramine on resistance of U251/TR cells to temozolomide / 中国药理学与毒理学杂志
Chinese Journal of Pharmacology and Toxicology ; (6): 620-626, 2016.
Article in Chinese | WPRIM | ID: wpr-492947
ABSTRACT
OBJECTIVE To examine the reversal effect of desipramine (DMI) on resistance to temozolomide(TMZ) in U251/TR cells and explore its mechanism. METHODS U251/TR cells were exposed to DMI (20-80μmol · L-1) or TMZ (0.5-10 mmol · L-1) for 24 h, cell viability was determined by cell counting kit-8 assay with IC50 calculated. The cytotoxicity of U251/TR cells treated with TMZ (1 or 2 mmol·L-1) in combination with DMI (20, 30 or 40 μmol · L-1) for 24 h was detected using CCK-8 assay. Synergism between DMI and TMZ was analyzed by the JIN Zheng-jun method. Apoptosis of U251/TR cells induced by TMZ 1 mmol · L-1, DMI 30 μmol · L-1,or their combination was examined by Hoechst33258 stains and caspase 3 activity was detected by luminescence analysis. Expression of C/EBP homologous protein (CHOP) was measured using quantitative real-time PCR and Western blotting. The survival rate of U251/TR cells treated with TMZ 1 mmol·L-1 and/or DMI 30μmol·L-1 was also assessed after silencing CHOP expression by small interference RNA (siRNA). RESULTS DMI or TMZ alone inhibited the growth of U251/TR cells significantly in a concentration-dependent manner (r 2=0.983,0.982,P1.15), ie, compared with TMZ alone, TMZ (1 mmol·L-1) com?bined with DMI (30 μmol · L-1) produced significant nuclear fragmentation and condensation (P< 0.05). In addition, DMI and TMZ in combination activated caspase 3 activity in U251/TR cells (P<0.05). Knock?down of CHOP by specific siRNA attenuated the synergistic effect of DMI in the presence of TMZ, the survival rate of the combined drug group raised from 51.8%to 62.2%(P<0.05). CONCLUSION The results suggest that DMI reverse resistance of U251/TR cells to TMZ through activation of the CHOP-depend?ently apoptosis pathway.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Pharmacology and Toxicology Year: 2016 Type: Article

Similar

MEDLINE

...
LILACS

LIS

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Pharmacology and Toxicology Year: 2016 Type: Article