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新城疫病毒增强阿霉素在宫颈癌小鼠模型中的抗肿瘤疗效。

Newcastle disease virus enhances the antitumor efficacy of Doxorubicin in a cervical cancer mouse model.

机构信息

Department of Molecular Cell Biology and Genetics, Bushehr Branch, Islamic Azad University, Bushehr, Iran.

Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical sciences, Tehran, Iran.

出版信息

BMC Cancer. 2024 Oct 10;24(1):1253. doi: 10.1186/s12885-024-13011-0.

Abstract

BACKGROUND AND AIMS

Cervical cancer (CC) is a common cancer among women, often treated with Doxorubicin (Doxo). Research is underway to explore the use of oncolytic virus (OV) therapy as a means to improve drug efficacy and enhance the immune system's tumor-fighting capabilities. Hence, our study purposes to evaluate the therapeutic potential of Newcastle disease virus (NDV) in increasing the antitumor efficacy of Doxo in mouse models of CC.

METHODS AND MATERIALS

TC1 cells were administered to C57BL/6 mice (Female) in a range of 6 to 8 weeks age (n = 40) to induce tumor growth. After tumor development, four treatment groups of mice were formed. Treatment were performed through NDV, Doxo, and a combination of both in three groups of treatment twice in a one-week intervention manner, while the control group treated with PBS. Following the last treatment, half of these mice were subjected to euthanize due to the immune-response assessment, and the other half were followed up till they died naturally in a certain period of time.

RESULTS

Mice that underwent the combined treatment showed significantly improved survival rates and slower tumor progression in comparison with the control group. This combined treatment substantially elevated nitric oxide (NO) and lactate dehydrogenase (LDH) levels in the splenocytes cultures of mice bearing cervical tumors. Furthermore, combination therapy resulted in a notable elevation in TNF-α, IL-12, and IFN-γ, secretion alongside a reduction in the release of TGF-β and IL-4 within the splenocytes in counter with the treatment of just NDV or Doxo.

CONCLUSION

According to the findings of this study, it seems that utilizing NDV can improve the effectiveness of Doxo in a mouse model of CC, suggesting it can serve as an adjunct therapy alongside chemotherapy.

摘要

背景和目的

宫颈癌(CC)是女性常见的癌症,常采用多柔比星(Doxo)治疗。目前正在研究使用溶瘤病毒(OV)治疗作为提高药物疗效和增强免疫系统抗肿瘤能力的一种方法。因此,我们的研究旨在评估新城疫病毒(NDV)在增加多柔比星在 CC 小鼠模型中的抗肿瘤疗效方面的治疗潜力。

方法和材料

将 TC1 细胞接种于 6 至 8 周龄 C57BL/6 小鼠(雌性)(n=40)以诱导肿瘤生长。肿瘤发展后,将小鼠分为四组治疗。治疗组分别采用 NDV、Doxo 以及两者联合的方式进行,每周两次,共进行两周期治疗,对照组采用 PBS 处理。最后一次治疗后,一半的小鼠因免疫反应评估而安乐死,另一半则在一段时间内自然死亡。

结果

与对照组相比,联合治疗组的小鼠存活率显著提高,肿瘤进展速度较慢。联合治疗组的荷瘤小鼠脾细胞培养中的一氧化氮(NO)和乳酸脱氢酶(LDH)水平显著升高。此外,联合治疗组 TNF-α、IL-12 和 IFN-γ 的分泌显著升高,而 TGF-β 和 IL-4 的释放显著降低,与单独使用 NDV 或 Doxo 治疗相比。

结论

根据本研究的结果,似乎使用 NDV 可以提高多柔比星在 CC 小鼠模型中的疗效,提示它可以作为化疗的辅助治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54f0/11465588/76739b027857/12885_2024_13011_Fig1_HTML.jpg

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