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溶瘤新城疫病毒AMHA1在乳腺癌三维培养模型中的抗转移和抗肿瘤活性

Antimetastatic and antitumor activities of oncolytic NDV AMHA1 in a 3D culture model of breast cancer.

作者信息

Al-Shammari Ahmed Majeed, Salman Marwa Ibrahim

机构信息

Experimental Therapy Department, Iraqi Center for Cancer and Medical Genetic Research, Mustansiriyah University, Baghdad, Iraq.

Department of Biotechnology, College of Science, University of Baghdad, Baghdad, Iraq.

出版信息

Front Mol Biosci. 2024 Aug 30;11:1331369. doi: 10.3389/fmolb.2024.1331369. eCollection 2024.

DOI:10.3389/fmolb.2024.1331369
PMID:39281317
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11392722/
Abstract

INTRODUCTION

Newcastle disease virus (NDV) AMHA1 is capable of killing cancer cells by direct replication or induction of apoptosis alongside other pathways. In this study, we report the potent antimetastatic and anticancer activities of NDV AMHA1 in a 3D spheroid model of breast cancer metastasis.

METHODS

we used two breast cancer cell lines AMJ13 and MCF7 in our metastasis model system.

RESULTS

First, we showed that NDV AMHA1 can infect and kill breast cancer cells in proliferating adherent cells and tumor spheroids using different virus doses and studying virus replication kinetics. We showed that NDV can infect and spread within the spheroids that represent metastasis before and after reattachment. Furthermore, we evaluated the ability of NDV to induce apoptosis in cancer spheroids and by virus tracking showed that NDV infection is essential for the elimination of these metastasis spheroids.

DISCUSSION

The mechanism by which NDV induces cell killing in the metastasis model is the induction of caspase-3 and P21 and inhibition of Ki67 in cancer cells, but not in normal cells. In conclusion, these results indicate that NDV AMHA1 has the ability to kill breast cancer metastases in suspension or attached, and this is a novel finding of NDV AMHA1 being a possibly efficient therapy against human metastatic breast cancer.

摘要

引言

新城疫病毒（NDV）AMHA1能够通过直接复制或诱导凋亡以及其他途径杀死癌细胞。在本研究中，我们报告了NDV AMHA1在乳腺癌转移的三维球体模型中的强大抗转移和抗癌活性。

方法

我们在转移模型系统中使用了两种乳腺癌细胞系AMJ13和MCF7。

结果

首先，我们表明NDV AMHA1可以使用不同的病毒剂量并研究病毒复制动力学，在增殖的贴壁细胞和肿瘤球体中感染并杀死乳腺癌细胞。我们表明NDV可以在代表重新附着前后转移的球体中感染并传播。此外，我们评估了NDV在癌球体中诱导凋亡的能力，并且通过病毒追踪表明NDV感染对于消除这些转移球体至关重要。

讨论

NDV在转移模型中诱导细胞杀伤的机制是诱导癌细胞中的半胱天冬酶-3和P21以及抑制Ki67，但在正常细胞中则不然。总之，这些结果表明NDV AMHA1具有杀死悬浮或附着的乳腺癌转移灶的能力，这是NDV AMHA1作为一种可能有效治疗人类转移性乳腺癌的新发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccf9/11392722/259e5aeaff1c/fmolb-11-1331369-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccf9/11392722/9b4f41b6f048/fmolb-11-1331369-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccf9/11392722/e1a60d808605/fmolb-11-1331369-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccf9/11392722/259e5aeaff1c/fmolb-11-1331369-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccf9/11392722/9b4f41b6f048/fmolb-11-1331369-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccf9/11392722/7577c70a67e2/fmolb-11-1331369-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccf9/11392722/eb2429b98ca3/fmolb-11-1331369-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccf9/11392722/1e0273a54d0a/fmolb-11-1331369-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccf9/11392722/23b41e3f7795/fmolb-11-1331369-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccf9/11392722/c51ee3119119/fmolb-11-1331369-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccf9/11392722/e1a60d808605/fmolb-11-1331369-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccf9/11392722/259e5aeaff1c/fmolb-11-1331369-g008.jpg

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