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Low-Intensity Ultrasound as a Novel Strategy to Improve the Cytotoxic Effect of Oncolytic Reovirus on Colorectal
Negar Sharifi1, Hoorieh Soleimanjahi1, Manijeh Mokhtari-Dizaji2
1Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Background:
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.
Methods:
L929 and CT26 cells were infected with reovirus T3D and were exposed to ultrasonic irradiation (1 MHz, 1 W/cm2, and 20% duty factor) for 10 s. The viruses' titer level of both groups was calculated in 2 types of cells by using the CCID50 method and compared with each other. Apoptosis, after 24 h, was measured by the flow cytometry method.
Result:
The results of CCID50 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.
Conclusion:
Due to the results of CCID50 and flow cytometry tests, low-intensity ultrasound increases the cytotoxicity level of reovirus in CT26 cells of the cellular colorectal cancer model.
Insights
Low-intensity ultrasound enhances the effectiveness of oncolytic reovirus (reovirus type 3 Dearing) in killing colorectal cancer cells. This combination therapy increases virus replication and induces greater apoptosis in cancer cells.
Area of Science:
- Oncology
- Virology
- Biophysics
Background:
- Colorectal cancer is a global health challenge, necessitating novel therapeutic strategies.
- Oncolytic viruses (OV), specifically reovirus type 3 Dearing (T3D), show promise for cancer treatment by inducing apoptosis.
- Low-intensity ultrasound is a safe physical agent that can enhance therapeutic interventions.
Purpose of the Study:
- To investigate the synergistic effect of low-intensity ultrasound and oncolytic reovirus T3D on colorectal cancer cells.
- To evaluate the impact of ultrasound on reovirus replication and cancer cell apoptosis.
Main Methods:
- Infection of L929 and CT26 cells with reovirus T3D.
- Exposure of infected cells to low-intensity ultrasound (1 MHz, 1 W/cm², 20% duty factor for 10 s).
- Quantification of virus titer using the Cell Culture Infectious Dose 50 (CCID50) assay.
- Measurement of apoptosis via flow cytometry 24 hours post-treatment.
Main Results:
- Ultrasound exposure significantly increased reovirus T3D titer in infected cells compared to unexposed controls.
- Flow cytometry analysis revealed a higher rate of apoptosis in cancer cells treated with both reovirus and ultrasound.
Conclusions:
- Low-intensity ultrasound potentiates the oncolytic activity of reovirus T3D against colorectal cancer cells.
- The combination of ultrasound and reovirus therapy demonstrates increased viral replication and cancer cell death.
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