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脂质体阿霉素联合溶瘤新城疫病毒对 4T1 细胞系的体外和体内作用评价:动物临床前研究。

Evaluation of the in vitro and in vivo effect of liposomal doxorubicin along with oncolytic Newcastle disease virus on 4T1 cell line: Animal preclinical research.

机构信息

Faculty of Specialized Veterinary Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Pediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran.

出版信息

Vet Med Sci. 2023 May;9(3):1426-1437. doi: 10.1002/vms3.1109. Epub 2023 Mar 15.

Abstract

BACKGROUND

Breast cancer is one of the most common malignancies in women, with one in 20 globally. Oncolytic viruses have recently been the first step in the biological treatment of cancer, either genetically engineered or naturally occurring. They increase specifically inside cancer cells and destroy them without damaging normal tissues or producing a host immune response against tumour cells or expressing transgenes. One of the most known members of this family is the Newcastle disease virus (NDV), a natural oncolytic virus that selectively induces apoptosis and DNA fragmentation in human cancer cells.

METHODS

This study performed biochemical and molecular investigations with variable doses of NDV (32, 64, 128 HAU) and liposomal doxorubicin (9 mg/kg) on mouse triple-negative mammary carcinoma cell line 4T1 and BALB/c models tumours for the first time.

RESULTS

Real-time quantitative PCR analysis in NDV-treated animal tumours showed increased expression of P21, P27 and P53 genes and decreased expression of CD34, integrin Alpha 5, VEGF and VEGF-R genes. Additional assessments in treated mouse models also showed that NDV increased ROS production, induced apoptosis, reduced tumour size and significantly improved prognosis, with no adverse effect on normal tissues.

CONCLUSIONS

These findings all together might indicate that NDV in combination with chemotherapy drugs could improve prognosis in cancer patients although many more conditions should be considered.

摘要

背景

乳腺癌是女性最常见的恶性肿瘤之一,全球每 20 人中就有 1 人患有乳腺癌。溶瘤病毒最近已成为癌症生物治疗的第一步,无论是基因工程还是天然存在的。它们在癌细胞内特异性增加,在不损伤正常组织或产生针对肿瘤细胞的宿主免疫反应或表达转基因的情况下破坏它们。该家族中最著名的成员之一是新城疫病毒(NDV),它是一种天然溶瘤病毒,可选择性诱导人类癌细胞凋亡和 DNA 片段化。

方法

本研究首次在鼠三阴性乳腺肿瘤细胞系 4T1 和 BALB/c 模型中用不同剂量的 NDV(32、64、128HAU)和脂质体阿霉素(9mg/kg)进行生化和分子研究。

结果

在 NDV 处理的动物肿瘤中进行的实时定量 PCR 分析显示,P21、P27 和 P53 基因的表达增加,而 CD34、整合素 Alpha 5、VEGF 和 VEGF-R 基因的表达减少。在治疗的小鼠模型中的进一步评估还表明,NDV 增加了 ROS 的产生,诱导了细胞凋亡,减少了肿瘤大小,并显著改善了预后,对正常组织没有不良影响。

结论

尽管还需要考虑许多其他条件,但这些发现可能表明 NDV 与化疗药物联合使用可以改善癌症患者的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fde0/10188073/e84bb39ccb7c/VMS3-9-1426-g003.jpg

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