TY - JOUR

T1 - Intratumoral Virotherapy with Wild-Type Newcastle Disease Virus in Carcinoma Krebs-2 Cancer Model

AU - Yurchenko, Kseniya S.

AU - Glushchenko, Alexandra V.

AU - Gulyaeva, Marina A.

AU - Bi, Yuhai

AU - Chen, Jianjun

AU - Shi, Weifeng

AU - Adamenko, Lyubov S.

AU - Shestopalov, Alexander M.

N1 - Publisher Copyright: Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/3/25

Y1 - 2021/3/25

N2 - The results of experimental and clinical trials of the agents based on oncolytic Newcastle disease virus (NDV) strains provided hope for the development of virotherapy as a promising method for treating human tumors. However, the mechanism of the antitumor effect of NDV and realization of its cytotoxic potential in a cancer cell remains to be elucidated. In the current work, we have studied the antitumor effect of NDV in a syngeneic model of mouse Krebs-2 carcinoma treated with intratumoral injections of a wild-type strain NDV/Altai/pigeon/770/2011. Virological methods were used for preparation of a virus-containing sample. Colorimetric MTS assay was used to assess the viability of Krebs-2 tumor cells infected with a viral strain in vitro. In vivo virotherapy was performed in eight-week-old male BALB/c mice treated with serial intratumoral injections of NDV in an experimental model of Krebs-2 solid carcinoma. Changes in the tumor nodes of Krebs-2 carcinoma after virotherapy were visualized by MRI and immunohistological staining. Light microscopy examination, immunohistochemical and morphometric analyses have shown that intratumoral viral injections contribute to the inhibition of tumor growth, appearance of necrosis-like changes in the tumor tissue and the antiangiogenic effect of the virus. It has been established that a course of intratumoral virotherapy with NDV/Altai/pigeon/770/2011 strain in a mouse Krebs-2 carcinoma resulted in increased destructive changes in the tumor tissue, in the volume density of necrotic foci and numerical density of endothelial cells expressing CD34 and VEGFR. These results indicate that intratumoral NDV injection reduces tumor progression of an aggressive tumor.

AB - The results of experimental and clinical trials of the agents based on oncolytic Newcastle disease virus (NDV) strains provided hope for the development of virotherapy as a promising method for treating human tumors. However, the mechanism of the antitumor effect of NDV and realization of its cytotoxic potential in a cancer cell remains to be elucidated. In the current work, we have studied the antitumor effect of NDV in a syngeneic model of mouse Krebs-2 carcinoma treated with intratumoral injections of a wild-type strain NDV/Altai/pigeon/770/2011. Virological methods were used for preparation of a virus-containing sample. Colorimetric MTS assay was used to assess the viability of Krebs-2 tumor cells infected with a viral strain in vitro. In vivo virotherapy was performed in eight-week-old male BALB/c mice treated with serial intratumoral injections of NDV in an experimental model of Krebs-2 solid carcinoma. Changes in the tumor nodes of Krebs-2 carcinoma after virotherapy were visualized by MRI and immunohistological staining. Light microscopy examination, immunohistochemical and morphometric analyses have shown that intratumoral viral injections contribute to the inhibition of tumor growth, appearance of necrosis-like changes in the tumor tissue and the antiangiogenic effect of the virus. It has been established that a course of intratumoral virotherapy with NDV/Altai/pigeon/770/2011 strain in a mouse Krebs-2 carcinoma resulted in increased destructive changes in the tumor tissue, in the volume density of necrotic foci and numerical density of endothelial cells expressing CD34 and VEGFR. These results indicate that intratumoral NDV injection reduces tumor progression of an aggressive tumor.

KW - carcinoma Krebs-2

KW - Newcastle disease virus

KW - oncolytic viruses

KW - tumor progression

KW - virotherapy

KW - Oncolytic viruses

KW - Carcinoma Krebs-2

KW - Tumor progression

KW - Virotherapy

UR - http://www.scopus.com/inward/record.url?scp=85103862721&partnerID=8YFLogxK

U2 - 10.3390/v13040552

DO - 10.3390/v13040552

M3 - Article

C2 - 33806229

AN - SCOPUS:85103862721

VL - 13

JO - Viruses

JF - Viruses

SN - 1999-4915

IS - 4

M1 - 552

ER -