Radiomodifying properties of a bromo-substituted derivative of indole-3-carboxylic acid in proton and electron therapy of Ehrlich carcinoma in vivo

Despite significant progress in the field of chemoradiation antitumor therapy, the introduction of new pharmacological agents and radiation response modifiers aimed at increasing the therapeutic index of radiation therapy remains one of the priority tasks of experimental oncology and radiobiology. Objective of the study is evaluation of the antitumor effects of the combined use of ionizing radiation (electrons, protons) and a new derivative of indole-3-carboxylic acid – 1-methyl-2-bromomethyl-3-ethoxycarbonyl-5-methoxy-6-bromindole. Materials and Methods: The study was conducted on female F1(CBA×C57Bl/6j) F1(CBAЧC57Bl/6j) mice with Ehrlich carcinoma transplanted into the right hind limb. The compound was administered intraperitoneally at a dose of 30 mg/kg on the day of irradiation and 48 hours after the first injection. The experimental methods included toxicometric and morphometric analyses. Results and Discussion: The median lethal dose of the compound was determined for intraperitoneal administration to mice, LD₅₀ = 60 mg/kg. Double injections in the monotherapy mode caused stable inhibition of tumor growth, which developed to 30 %. The combined use of radiation exposure and the studied compound led to significant increasing of therapeutic efficacy indicating the presence of synergistic interaction: the tumor growth inhibition index increased by 19 % with single electron irradiation, by 32 % with fractionated electron irradiation, and by 27 % with single proton irradiation. In addition, the experimental combination therapy, along with significant suppression of tumor growth, increased the survival of tumor-bearing animals without causing significant toxic effects. Conclusion: The obtained results indicate the prospects for further study of combined regimens of radiation therapy and indole-3-carbinol derivatives. Further studies of the mechanisms of interaction of these compounds and ionizing radiation should include an assessment of the effect on the main pathophysiological mechanisms of neoplasia development, key pathways of DNA repair and apoptosis.

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