Low-Intensity Ultrasound as a Novel Strategy to Improve the Cytotoxic Effect of Oncolytic Reovirus on Colorectal Cancer Model Cells

Abstract

<b><i>Background:</i></b> Colorectal cancer is the third most common cancer all over the world, so in the battle to fight this hurdle, new therapeutic approaches such as oncolytic viruses (OV) have attracted much attention because of the fact that they can inherently kill cancer cells. Oncolytic reovirus is one of the candidates for treatment as a nonpathogenic species specially reovirus type 3 Dearing (T3D), which can induce apoptosis. To speed up the entry and function of the reovirus, low-intensity ultrasound, which is a safe system for damage to the cells and tissues, is a promising approach to be used in combination with other therapeutic approach. <b><i>Methods:</i></b> L929 and CT26 cells were infected with reovirus T3D and were exposed to ultrasonic irradiation (1 MHz, 1 W/cm<sup>2</sup>, and 20% duty factor) for 10 s. The viruses’ titer level of both groups was calculated in 2 types of cells by using the CCID<sub>50</sub> method and compared with each other. Apoptosis, after 24 h, was measured by the flow cytometry method. <b><i>Result:</i></b> The results of CCID<sub>50</sub> in infected cells were exposed to low-intensity ultrasound showed an increased virus titer compared with unexposed infected cells. Moreover, according to the results of the flow cytometry test, it was found that the amount of apoptosis in infected cells that are exposed to low-intensity ultrasound waves is higher than those infected cells. <b><i>Conclusion:</i></b> Due to the results of CCID<sub>50</sub> and flow cytometry tests, low-intensity ultrasound increases the cytotoxicity level of reovirus in CT26 cells of the cellular colorectal cancer model.