Potentiating Effect of Nitric Oxide Donor on Antitumor Activity of Doxorubicin in Glioblastoma-Bearing Rats

Abstract

The objective of the study was to investigate the influence of the NO donor nitroglycerin (NG) on the antitumour effect of doxorubicin (Dox) in rats with the intracranially implanted 101.8 glioblastoma. Materials and methods. Male Wistar rats with the implanted 101.8 glioblastoma were treated with the following formulations (n=15-19): doxorubicin (Dox, 1.5 mg/kg, i.v.), nitroglycerin (NG, 5 mg/kg, oil solution, topical), and a combination of doxorubicin and nitroglycerin (Dox+NG: 1.5 mg/kg and 5 mg/kg, respectively) on 2nd, 5th, and 8th day after tumor implantation. The tumor size was measured on the histological sections of the brain on the 14th day (n=6-9). The remaining animals were followed up for survival for 100 days. Untreated animals were used as control (n=22). Results. The antitumor effect was evaluated by the increase in life expectancy (ILE, %) and tumor growth inhibition (TGI, %) relative to untreated animals in control group. The increased life expectancy was observed in all groups. The maximal effect was achieved in the Dox+NG group: ILE 176%, TGI 89%. In the Dox group, the ILE was 130% and TGI was 75%. Nitroglycerin alone produced the ILE of 130%. Conclusion. Nitric oxide donor nitroglycerin considerably potentiated the antitumor activity of doxorubicin against the intracranial glioblastoma in rats. This phenomenon is most probably explained by the increased penetration of doxorubicin into the tumor due to the enhanced permeability of the cerebral endothelium produced by NO generated by nitroglycerin.

Keywords

• nitroglycerin
• doxorubicin
• glioblastoma 101.8