Combination of nanosomal form of doxorubicin, interferon alpha, and nitroglycerin in the threatment of 101.8 glioblastoma in Wistar rats

Abstract

The search for effective approaches to the treatment of patients with glioblastoma is one of the difficult tasks of neurooncology; standard methods of therapy show limited results. Combined therapy, which includes different antitumor mechanisms, can increase its effectiveness. The combination of PLGA nanoform of doxorubicin (Dox-PLGA), antitumor cytokine — interferon alfa (IFN-α), and nitrogen oxide (NO) donor nitroglycerin (NG) was investigated in this work both in vitro (rat C6 glioma) and in vivo (rat 101.8 glioblastoma). MTT assay in the C6 cell line showed great cytotoxicity and antiproliferative effect of the combination of IFN-α with Dox-PLGA and NG. The lowest tumour cell survival was observed when using a high dose of IFN-α (10 ng/ml) in mono-mode. In the in vivo experiment, 32 female Wistar rats with 101.8 glioblastoma received therapy in the following modes: Dox-PLGA + NG; Dox-PLGA + IFN-α; Dox- PLGA + IFN-α + NG. There was a significant increase in median survival and life expectancy (ILE) in all groups receiving therapy compared to the group that did not undergo treatment. The longest median lifespan (27 days), survival up to 100 days (1 animal), ILE (131%) were observed in animals that received the combination Dox-PLGA + IFN-α+ NG, compared to the group without treatment, in which the median lifespan was 15 days. Thus, the therapy of experimental glioblastoma both in vivo and in vitro with the combination of Dox-PLGA + IFN-α + NG has the most pronounced therapeutic and antitumor effect, which must be taken into account when developing new more effective methods of treating human glioblastomas.