Effect of Low Molecular Weight Pectin and Metformin on the Antitumour Effect of Chemopreventive Agents in Rats with Walker's Carcinosarcoma

Abstract

Introduction and Objective: Currently, the increase in the effectiveness of antitumour treatment of patients with oncological pathology of various localizations is associated with the use of multicomponent chemotherapy regimens. However, the cost of innovative drugs is excessively high and, according to experts of the World Health Organisation, no state is able to fully compensate patients for the costs of treatment with immunological agents. Therefore, there is growing interest in evidence-based pharmacocorrection as a promising way to improve the effectiveness of anti-blastoma treatment. According to the results of numerous screening studies it was found that flavonoids, alkaloids, glycosides can be used to suppress the growth of the main tumour node and dissemination process both at isolated administration and in combination with cytostatics, and water-soluble polysaccharides turned out to be the most effective. One plant remedy is low molecular weight pectin. Pectins have been found to have not only antitumour potential, but also the ability to enhance the antitumour activity of conventional cytostatics. The aim of the study is to improve the efficacy of conventional therapies for malignant diseases.

Materials and methods: The main research methods included determination of antitumour activity of preparations on models of transplanted rat tumours, morphologically and statistically. Experimental therapy was carried out on white mongrel rats and Wistar rats. The tumour was transplanted subcutaneously. Pectin and metformin were administered by probe, intragastrically. Cytostatics were administered intraperitoneally. Antitumour activity was assessed by TGI (tumour growth inhibition), ILE (increased life expectancy) and ALE (average life expectancy).

Results: The combination of metformin, pectin and chemopreparations (methotrexate and oxaliplatin) resulted in a significant antitumour effect with an increase in life expectancy. The combination of metformin and pectin with methotrexate increased the life expectancy of animals, whereas in monotherapy animals died earlier than in the control group without treatment, which indicates the ability of the combination to reduce the toxicity of cytostatics. Combinations of pectin + paclitaxel and metformin + paclitaxel showed significant antitoxic effect. When doxorubicin was combined with pectin, the TGI was 65.89 and 62.64%, which is quite high in the therapy of Walker carcinosarcoma.  In experiments with fluorouracil, high doses of the drug proved toxic to tumour-bearing animals. The combination of fluorouracil with metformin showed the best TGI and ILE rates (80.65% and 89.9%, respectively). The combination of fluorouracil with pectin showed high TGI (59.7). For the combination of pectin + gemcitabine at a dosage of 50mg/kg, the TGI (89.5% to 98.48% on days 9 and 21) and ILE (134.26%) showed a mutual influence of the drugs' properties in the direction of enhancing the antitumour effect, whereas the gemcitabine monotherapy showed lower rates (TGI 66.2% and ILE 80.21%). The combination of all 3 drugs had a good antitumour effect at gemcitabine dosage of 25mg/kg (TGI - 83.05%, ILE - 157.3%), whereas at gemcitabine dosage of 50mg/kg the TGI was 49.3% and ILE - 15.73%. Similar conclusions can be drawn when etoposide was combined with pectasol. At high TGI at the beginning of the experiments with both monotherapy and drug combination, the survival rate of rats was higher when pectasol was administered in combination with etoposide.