1. The Effect of Therapy Regimen on Antitumor Efficacy of the Nanosomal Doxorubicin against Rat Glioblastoma 101.8.
- Author
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Alekseeva AI, Khalansky AS, Miroshnichenko EA, Gerasimov AD, Sentyabreva AV, Kudelkina VV, Osipova NS, Gulyaev MV, Gelperina SE, and Kosyreva AM
- Subjects
- Animals, Rats, Polylactic Acid-Polyglycolic Acid Copolymer chemistry, Antibiotics, Antineoplastic pharmacology, Antibiotics, Antineoplastic therapeutic use, Male, Cell Line, Tumor, Brain Neoplasms drug therapy, Brain Neoplasms pathology, Polyglycolic Acid chemistry, Gene Expression Regulation, Neoplastic drug effects, Glioblastoma drug therapy, Glioblastoma pathology, Doxorubicin pharmacology, Doxorubicin therapeutic use, Nanoparticles chemistry
- Abstract
One of the key problems of glioblastoma treatment is the low effectiveness of chemotherapeutic drugs. Incorporation of doxorubicin into PLGA nanoparticles allows increasing the antitumor effect of the cytostatics against experimental rat glioblastoma 101.8. Animal survival, tumor volume, and oncogene expression in tumor cells were compared after early (days 2, 5, and 8 after tumor implantation) and late (days 8, 11, and 14) start of the therapy. At late start, a significant increase in the expression of oncogenes Gdnf, Pdgfra, and Melk and genes determining the development of multidrug resistance Abcb1b and Mgmt was revealed. At early start of therapy, only the expression of oncogenes Gdnf, Pdgfra, and Melk was enhanced. Early start of treatment prolonged the survival time and increased tumor growth inhibition by 141.4 and 95.7%, respectively, in comparison with the untreated group; these differences were not observed in the group with late start of therapy. The results indicate that the time of initiation of therapy is a critical parameter affecting the antitumor efficacy of DOX-PLGA., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
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