Antitumor efficiency of sonodynamic therapy in combination with chlorine-based photosensitizer in experiments

Abstract

Introduction. Sonodynamic therapy is a topical research area in experimental oncology. The method is based on the combined use of photosensitizing agents with ultrasonic radiation with certain parameters. The result of this interaction is the induction of sonochemical reactions and the effect of cavitation in the tumor cell. The consequence is its death (apoptosis, autophagy).The study objective is to investigate the antitumor efficacy of sonodynamic therapy with a chlorine-based photosensitizer (PS) in an experiments on laboratory animals with transplantable tumors.Materials and methods. The experimental study was performed on 50 white outbred rats weighing 250 ± 50 grams. Subcutaneously transplanted Pliss lymphosarcoma (PLS) and alveolar liver cancer RS1 (RS1) were used as tumor models. Chlorine-based PS (Belmedpreparaty, Republic Belarus) was injected intravenously at a dose of 2.5 mg / kg. The ultrasound sessions (US) were carried out 2.5–4 hours (depending on the tumor strain) after the administration of the PS using the device Phyaction U (Gymna Yniphy, Belgium) with frequencies of 1.04 and 3 MHz, intensity of 2 W / cm2 and duration of 10 minutes in continuous mode. For each of the tumor model the study was performed on 25 laboratory animals subdivided into groups of 5 individuals: intact control, US 1.04 MHz; US 3 MHz; PS + US 1.04 MHz and PS + US 3 MHz. The criteria for assessing the antitumor efficacy were indicators of the dynamics of the growth of transplanted tumors: аverage volume of tumors (Vav, cm3), the coefficient of tumor growth inhibition (TGI, %), coefficient of absolute growth of tumors (K) and the frequency of complete regressions 60 days after treatment (%).Results. For PLS Vav in groups were 32.72 ± 7.23; 26.81 ± 1.06; 14.80 ± 5.08; 9.37 ± 6.05 and 22.25 ± 4.91 cm3, respectively (p ˂0.05). The coefficients TGI in the experimental groups were 20.27; 54.77; 71.36 and 31.99 %, respectively. Indicators K in groups were 21.64; 14.52; 6.12; 4.91 and 15.34, respectively. The frequency of complete tumor regressions 60 days after the start of the experiment was 0, 20, 20, 40 and 0 %, respectively. For RS1 Vav in groups were 23.29 ± 5.11; 6.22 ± 2.22; 11.78 ± 4.57; 6.38 ± 2.57 and 13.06 ± 3.53 cm3, respectively (p ˂0.05). The coefficient of TGI in the experimental groups were 73.25; 49.42; 72.60 and 43.92 %, respectively. Indicators K in groups were: 8.34; 1.11; 3.39; 2.91 and 5.05, respectively. The frequency of complete tumor regressions 60 days after the start of the experiment was 0, 0, 0, 40 and 0 %, respectively.Conclusions. The data obtained indicate a trend towards an increase in the antitumor effectiveness of the combined use of PS and sonodynamic therapy on various histological structures and growth patterns of transplanted tumors, as well as the prospects for further studies of the sonosensitizing properties of photosensitizing agents.