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新城疫病毒病毒疗法:揭示溶瘤疗效与免疫调节作用

Newcastle Disease Virus Virotherapy: Unveiling Oncolytic Efficacy and Immunomodulation.

作者信息

Zaher Kawther A, Alrahimi Jehan S, Basingab Fatemah S, Aldahlawi Alia M

机构信息

Immunology Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

出版信息

Biomedicines. 2024 Jul 5;12(7):1497. doi: 10.3390/biomedicines12071497.

Abstract

UNLABELLED

In virotherapy, cancer cells are eradicated via viral infection, replication, and dissemination (oncolysis).

BACKGROUND

This study aims to evaluate the oncolytic potential of Newcastle disease virus (NDV) against colon cancer and explore the immune response associated with its therapeutic effects.

METHODS

NDV was tested for its oncolytic potential in colon cancer cell lines using MTT assays and apoptosis assessments. Tumor-induced mice were treated with NDV, tumor cell lysate (TCL), or a combination of both. After the euthanasia of murine subjects, an assessment of oncolytic efficacy was performed through flow cytometry analysis of murine blood and tumor tissue, targeting CD83, CD86, CD8, and CD4. An ELISA was also performed to examine interferon-gamma levels, interleukin-4 levels, interleukin-12 levels, and interleukin-10 levels in serum and spleen homogenate.

RESULTS

Cell viability was low in HCT116 and HT-29, indicating a cytotoxic effect in the MTT assay. NDV+TCL recorded the highest rate of cell death (56.72%). NDV+TCL had accelerated cell death after 48 h, reaching 58.4%. The flow cytometry analysis of the blood and tumor of mice with induced tumor treated with combined treatment revealed elevated levels of CD83, CD86, CD8, and CD4 (76.3, 66.9, 83.7, and 14.4%, respectively). The ELISA levels of IFN-γ, IL-4, and IL-12 in serum and the spleen homogenate were elevated (107.6 ± 9.25 pg/mL). In contrast, the expression of IL-10 was significantly reduced (1 ± 0.79).

摘要

未标记

在病毒疗法中,癌细胞通过病毒感染、复制和扩散(溶瘤作用)被根除。

背景

本研究旨在评估新城疫病毒(NDV)对结肠癌的溶瘤潜力,并探索与其治疗效果相关的免疫反应。

方法

使用MTT法和凋亡评估检测NDV在结肠癌细胞系中的溶瘤潜力。用NDV、肿瘤细胞裂解物(TCL)或两者的组合处理诱导肿瘤的小鼠。在对小鼠实施安乐死后,通过对小鼠血液和肿瘤组织进行流式细胞术分析来评估溶瘤效果,检测指标为CD83、CD86、CD8和CD4。还进行了酶联免疫吸附测定(ELISA)以检测血清和脾脏匀浆中的干扰素-γ水平、白细胞介素-4水平、白细胞介素-12水平和白细胞介素-10水平。

结果

在HCT116和HT-29细胞中细胞活力较低,表明在MTT试验中有细胞毒性作用。NDV+TCL记录的细胞死亡率最高(56.72%)。48小时后,NDV+TCL加速了细胞死亡,达到58.4%。对联合治疗的诱导肿瘤小鼠的血液和肿瘤进行流式细胞术分析显示,CD83、CD86、CD8和CD4水平升高(分别为76.3%、66.9%、83.7%和14.4%)。血清和脾脏匀浆中IFN-γ、IL-4和IL-12的ELISA水平升高(107.6±9.25 pg/mL)。相比之下,IL-10的表达显著降低(1±0.79)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0d8/11274839/500479ef8414/biomedicines-12-01497-g001.jpg

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