体外和体内评价环磷酰胺与溶瘤性新城疫病毒(NDV)的作用:动物临床前研究

Mohammad Reza Foroughi-Gilvaee, Alireza Jahandideh, Mohammad Faranoush, Reza Nekouian
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引用次数: 0

摘要

背景 乳腺癌是全球死亡的主要原因。溶瘤病毒疗法是一种很有前景的治疗方式,它能直接破坏癌细胞并诱导针对癌细胞的免疫反应。在天然溶瘤病毒中,新城疫病毒(NDV)具有选择性肿瘤细胞感染的特性。 材料与方法 本研究首次探讨了不同剂量的 NDV 和环磷酰胺对 4T1 癌细胞系和 BALB/c 小鼠肿瘤的疗效。 结果 与对照组相比,NDV 和环磷酰胺联合治疗组的 P21、P27 和 P53 基因表达水平分别显著增加了 38%、46% 和 81%(p <0.05)。相比之下,CD34、整合素α5、血管内皮生长因子(VEGF)和血管内皮生长因子受体(VEGFR)基因的表达水平则明显下降,降幅分别为 47%、45%、42% 和 23% (p <0.05)。用 2′,7′-二氯二氢荧光素二乙酸酯(DCFH-DA)染色进行的活性氧(ROS)生成测定显示,与未处理组相比,经 NDV 处理的 4T1 细胞中的 ROS 水平在 24 小时后明显增加(p <0.01)。此外,Annexin V/碘化丙啶(PI)双染色分析表明,6 小时和 12 小时后,NDV 处理组的凋亡细胞比例分别下降了 0.61% 和 1.63%(p <0.05)。12 天后,NDV 治疗组的肿瘤体积减少了 72%-87%,而对照组则增加了 48%,反映了肿瘤体积相对于对照组的净减少(p <0.001)。 结论 这些研究结果表明,NDV 与化疗药物联用可能是癌症患者的一种有前途的治疗选择。然而,还需要考虑其他一些因素。这些结果表明,NDV 可能对癌症治疗具有潜在作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

In vitro and in vivo evaluation of the cyclophosphamide effect along with oncolytic Newcastle disease virus (NDV): An animal preclinical research

In vitro and in vivo evaluation of the cyclophosphamide effect along with oncolytic Newcastle disease virus (NDV): An animal preclinical research

Background

Breast cancer is a major cause of mortality globally. Oncolytic virotherapy is a promising treatment modality that directly destroys cancer cells and induces an immune response against them. Among natural oncolytic viruses, Newcastle disease virus (NDV) has shown selective tumor cell infection.

Materials and methods

In this study, we investigated the efficacy of variable doses of NDV and cyclophosphamide on 4T1 cancer cell line and BALB/c mouse tumors for the first time.

Results

Compared with the control group, the combination treatment group with NDV and cyclophosphamide showed a significant increase in the expression levels of P21, P27, and P53 genes by 38%, 46%, and 81%, respectively (p < 0.05). In contrast, the expression levels of CD34, integrin α5, vascular endothelial growth factor (VEGF), and vascular endothelial growth factor receptor (VEGFR) genes significantly decreased by 47%, 45%, 42%, and 23%, respectively (p < 0.05). The reactive oxygen species (ROS) generation assay evaluated with 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) staining showed a significant increase in ROS levels within 4T1 cells treated with NDV compared with the untreated group after 24 h (p < 0.01). Furthermore, Annexin V/propidium iodide (PI) double staining analysis showed that the proportion of apoptotic cells in the NDV-treated group decreased by 0.61% and 1.63% after 6 h and 12 h, respectively (p < 0.05). After 12 days, tumor volume in the NDV-treated groups decreased by 72%−87% compared with a 48% increase in the control group, reflecting a net reduction in tumor volume relative to the control group (p < 0.001).

Conclusion

These findings demonstrate that NDV in combination with chemotherapy drugs may be a promising therapeutic option for cancer patients. However, several other factors need to be considered. These results indicate that NDV may have potential effects on cancer treatment.

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