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Registration Number

0219U001621, 0115U005384 , R & D reports

Title

Development of target cancer therapy based on the combined use of energy metabjlism inhibitors of malignant cells

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Head

Solyanik Galina Ivanivna, Доктор фізико-математичних наук

Registration Date

12-02-2019

Organization

R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology

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It was shown that DCA in combination with glycolysis inhibitor 2-DG resulted in significant inhibition of LLC/R9 (a high angiogenic counterpart of Lewis lung carcinoma) primary tumor growth up to 71%. Whereas, DCA alone did not affect primary tumor growth. Anticancer action of combinative therapy correlated with statistically reliable activation of tumor-associated macrophages and a substantial lactate level reduction inside the tumor. For the first time it was found that the DCA in combination with both the 2-DG and MFM (despite monotherapy thereof) showed significant antitumor activity against glioma C6, statistically increasing the life span of tumor bearing rats by more than 44%. It was revealed that the effectiveness of combination therapy correlated with the 3-fold stimulation of tumor cell apoptosis in vitro, that was confirmed by the results obtained in histological investigation of tumor tissues from animals fed per os DCA in combination with MFM. High antitumor activity DCA in combination with MFM was associated with a significant inhibition of glycolysis, as evidenced by statistically reliable decrease of glucose consumption rate by glioma C6 cells in vitro, and decrease of glucose in blood of tumor bearing rats after combined therapy. The results have fundamental significance and build the basis for the clinical trials on combined DCA, 2-DG and MFM use for treatment of malignant tumors of the brain. The results of the research were published in 11 national, foreign and international magazines (all indexed in Scopus and Web of Science) and were presented at the 11 scientific conferences; also it was registered as a patent application for the invention.

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Колесник Д.Л.
Прохорова І.В.
Пясковська О.М.
Святецька В.М.
Федорчук О.Г.
Хаєцький І.К.
Храновська Н.М.
Юрченко О.В.
Якшибаєва Ю.Р.