Department of Ophthalmology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
Hereditas. 2024 Sep 28;161(1):36. doi: 10.1186/s41065-024-00337-9.
The therapeutic potential of oncolytic measles virotherapy has been demonstrated across various malignancies. However, the effectiveness against human breast cancer (BC) and the underlying mechanisms of the recombinant measles virus vaccine strain Hu191 (rMeV-Hu191) remain unclear.
We utilized a range of methods, including cell viability assay, Western blot, flow cytometry, immunofluorescence, SA-β-gal staining, reverse transcription quantitative real-time PCR, transcriptome sequencing, BC xenograft mouse models, and immunohistochemistry to evaluate the antitumor efficacy of rMeV-Hu191 against BC and elucidate the underlying mechanism. Additionally, we employed transcriptomics and gene set enrichment analysis to analyze the lipid metabolism status of BC cells following rMeV-Hu191 infection.
Our study revealed the multifaceted antitumor effects of rMeV-Hu191 against BC. rMeV-Hu191 induced apoptosis, inhibited proliferation, and promoted senescence in BC cells. Furthermore, rMeV-Hu191 was associated with changes in oxidative stress and lipid homeostasis in infected BC cells. In vivo, studies using a BC xenograft mouse model confirmed a significant reduction in tumor growth following local injection of rMeV-Hu191.
The findings highlight the potential of rMeV-Hu191 as a promising treatment for BC and provide valuable insights into the mechanisms underlying its oncolytic effect.
溶瘤麻疹病毒治疗在多种恶性肿瘤中显示出了治疗潜力。然而，重组麻疹病毒疫苗株 Hu191（rMeV-Hu191）对人乳腺癌（BC）的有效性及其潜在机制尚不清楚。
我们采用了一系列方法，包括细胞活力测定、Western blot、流式细胞术、免疫荧光、SA-β-gal 染色、逆转录定量实时 PCR、转录组测序、BC 异种移植小鼠模型和免疫组织化学，来评估 rMeV-Hu191 对 BC 的抗肿瘤疗效，并阐明其潜在机制。此外，我们还采用转录组学和基因集富集分析来分析 rMeV-Hu191 感染后 BC 细胞的脂质代谢状态。
我们的研究揭示了 rMeV-Hu191 对 BC 的多方面抗肿瘤作用。rMeV-Hu191 诱导 BC 细胞凋亡、抑制增殖并促进衰老。此外，rMeV-Hu191 与感染的 BC 细胞中氧化应激和脂质平衡的变化有关。在体内，使用 BC 异种移植小鼠模型的研究证实，局部注射 rMeV-Hu191 可显著抑制肿瘤生长。
这些发现强调了 rMeV-Hu191 作为 BC 治疗的潜在治疗方法的潜力，并为其溶瘤作用的潜在机制提供了有价值的见解。
