Jafari Mahdie, Abdoli Shahriyar, Asgari Majid, Moghaddam Pour Masoud, Shokrgozar Mohammad Ali, Sharifzadeh Zahra
Department of Immunology, Pasteur Institute of Iran, Tehran, Iran.
Student Research Committee, Pasteur Institute of Iran, Tehran, Iran.
Iran Biomed J. 2025 Jan 1;29(1 & 2):9-19. doi: 10.61186/ibj.4367.
Despite existing treatments, advanced solid tumors, such as prostate cancer (PCa), require the development of novel anticancer therapies. Oncolytic viruses (OVs) present a potential treatment option for solid tumors. Newcastle disease virus (NDV) is one of the most promising OVs that can replicate within and destroys human cancer cells. This study aimed to evaluate the cytotoxic and apoptotic effects of the NDV strain on human PCa cells in vitro. Additionally, We examined a novel treatment for PCa by combining Lenalidomide (Len) with NDV.
NDV strains La Sota, B1, and I2 were tested for cytotoxicity against several cell lines. A safety assessment was conducted in primary cells using peripheral blood mononuclear cells (PBMCs). Also, apoptosis induction was measured using annexin V/7AAD staining. Finally, the cytotoxic effects of NDV alone and in combination with Len, were assessed using MTT.
The NDV showed cytotoxic effects on tumor cell lines and induced apoptosis in infected prostate cells compared to control cells. The NDV La Sota strain exhibited significant oncolytic capacity, reducing the viability of LNCaP and DU145 cells to less than 40% at specific concentrations, while showing no cytotoxic effects on primary PBMCs. Also, NDV induced apoptosis in the prostate cell line by 60%. Furthermore, Len enhanced the cytotoxicity of PCa cells when combined with NDV.
Our study confirms the efficacy of oncolytic NDV treatment for PCa, particularly utilizing the La Sota strain. When combined with Len, NDV indicates an enhanced effectiveness in destroying tumor cells. These findings suggest a prospective treatment approach that needs more preclinical and clinical studies to improve outcomes in PCa treatment.
尽管现有治疗方法存在,但前列腺癌(PCa)等晚期实体瘤仍需要开发新的抗癌疗法。溶瘤病毒(OVs)为实体瘤提供了一种潜在的治疗选择。新城疫病毒(NDV)是最有前景的溶瘤病毒之一,能够在人类癌细胞内复制并将其破坏。本研究旨在评估NDV毒株对人PCa细胞的体外细胞毒性和凋亡作用。此外,我们研究了来那度胺(Len)与NDV联合用于PCa的新型治疗方法。
检测NDV毒株La Sota、B1和I2对几种细胞系的细胞毒性。使用外周血单个核细胞(PBMCs)对原代细胞进行安全性评估。此外,采用膜联蛋白V/7-氨基放线菌素D(7AAD)染色法检测细胞凋亡情况。最后,使用MTT法评估单独使用NDV以及NDV与Len联合使用的细胞毒性作用。
与对照细胞相比,NDV对肿瘤细胞系具有细胞毒性作用,并能诱导感染的前列腺细胞发生凋亡。NDV La Sota毒株表现出显著的溶瘤能力,在特定浓度下可将LNCaP和DU145细胞的活力降低至40%以下,而对原代PBMCs无细胞毒性作用。此外,NDV可诱导前列腺细胞系凋亡60%。而且,Len与NDV联合使用时可增强PCa细胞的细胞毒性。
我们的研究证实了溶瘤性NDV治疗PCa的有效性,尤其是使用La Sota毒株时。当与Len联合使用时,NDV在破坏肿瘤细胞方面显示出增强的效果。这些发现提示了一种前瞻性的治疗方法,需要更多的临床前和临床研究来改善PCa治疗的效果。