Poorghobadi Shima, Hosseini Seyed Younes, Sadat Seyed Mehdi, Abdoli Asghar, Irani Shiva, Baesi Kazem
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Biochem Genet. 2025 Feb;63(1):315-330. doi: 10.1007/s10528-024-10671-2. Epub 2024 Mar 4.
Multiple myeloma is a type of malignant neoplasia whose treatment has changed over the past decade. This study aimed to investigate the effects of combination of Adenovector-carrying interleukin-24 and herpes simplex virus 1 thymidine kinase/ganciclovir on tumor growth, autophagy, and unfolded protein response mechanisms in mouse model of multiple myeloma. Six groups of mice, including Ad-HSV-tk/GCV, Ad-IL-24, Ad-HSV-tk/IL-24, Ad-GFP, and positive and negative controls, were investigated, and each group was injected every 72 h. The tumor size was measured several times. The expression of LC3B evaluated through western blotting and ASK-1, CHOP, Caspase-3, and ATF-6 genes in the UPR and apoptosis pathways were also analyzed by the quantitative polymerase chain reaction (qPCR) method. The present results showed that the injection of Ad-HSV-tk/GCV, Ad-HSV-tk/IL-24, and metformin reduced the tumor size. The expression of LC3B was significantly higher in the treatment groups and positive control groups compared to the negative control group. The expression of CHOP, caspase-3, and ATF-6 genes was significantly higher in the Ad-IL-24 group compared to the other treatment groups. Besides, the ASK-1 expression was significantly lower in the Ad-IL-24 group as compared to the other groups. Overall, the results indicated that the presence of the HSV-tk gene in the adenovectors reduced the size of tumors and induced autophagy by triggering the expression of LC3B protein. The presence of the IL-24 might affect tumor growth but not as much the therapeutic effect of HSV-tk. Furthermore, the results indicated that co-administration of IL-24 and HSV-tk had no synergistic effect on tumor size control.
多发性骨髓瘤是一种恶性肿瘤，其治疗方法在过去十年中发生了变化。本研究旨在探讨携带白细胞介素-24的腺病毒载体与单纯疱疹病毒1胸苷激酶/更昔洛韦联合应用对多发性骨髓瘤小鼠模型肿瘤生长、自噬和未折叠蛋白反应机制的影响。研究了六组小鼠，包括Ad-HSV-tk/GCV、Ad-IL-24、Ad-HSV-tk/IL-24、Ad-GFP以及阳性和阴性对照组，每组每72小时注射一次。多次测量肿瘤大小。通过蛋白质免疫印迹法评估LC3B的表达，并通过定量聚合酶链反应（qPCR）方法分析未折叠蛋白反应和凋亡途径中ASK-1、CHOP、Caspase-3和ATF-6基因的表达。目前的结果表明，注射Ad-HSV-tk/GCV、Ad-HSV-tk/IL-24和二甲双胍可减小肿瘤大小。与阴性对照组相比，治疗组和阳性对照组中LC3B的表达明显更高。与其他治疗组相比，Ad-IL-24组中CHOP、Caspase-3和ATF-6基因的表达明显更高。此外，与其他组相比，Ad-IL-24组中ASK-1的表达明显更低。总体而言，结果表明腺病毒载体中HSV-tk基因的存在通过触发LC3B蛋白的表达减小了肿瘤大小并诱导了自噬。IL-24的存在可能会影响肿瘤生长，但对HSV-tk的治疗效果影响不大。此外，结果表明IL-24和HSV-tk联合给药对肿瘤大小控制没有协同作用。
