Yoon Wonsuck, Park Yongsung, Kim Seunghyun, Park Yongkeun, Kim Chul Yong
Allergy Immunology Center, College of Medicine, Korea University, Seoul 02841, Korea.
Department of Life Science and Biotechnology, Korea University, Seoul 02841, Korea.
Microorganisms. 2021 Nov 22;9(11):2408. doi: 10.3390/microorganisms9112408.
Anticancer treatment strategies using bacteria as a vector are currently expanding with the development of anticancer drugs. Here, we present a research strategy to develop anticancer drugs using bacteria that contain miRNAs. We also present a strategy for the development of novel bacterial anticancer drugs in combination with radiation. strains expressing miRNA were produced by modifying the miRNA expression vector encoding INHA, a radiation-resistant gene developed previously. The anticancer effect of INHA was confirmed using skin cancer cell lines. We also tested a combination strategy comprising bacteria and radiation for its anticancer efficacy against radiation-resistant mouse melanoma to increase the efficacy of radiation therapy as a novel strategy. The recombinant strain was confirmed to promote effective cell death even when combined with radiation therapy, which exerts its cytotoxicity by enhancing reactive oxygen species production. Moreover, a combination of bacterial and radiation therapy enhanced radiotherapy efficacy. When combined with radiation therapy, bacterial therapy exhibited effective anti-cancer properties even when administered to animals harboring radiation-resistant tumors. This strategy may promote the secretion of cytokines in cells and more effectively reduce the number of bacteria remaining in the animal. Thus, this study may lead to the development of a strategy to improve the effectiveness of radiation therapy using expressing cancer-specific miRNA for intractable cancers such as those resistant to radiation.
随着抗癌药物的发展，以细菌为载体的抗癌治疗策略目前正在不断扩展。在此，我们提出一种利用含有微小RNA（miRNA）的细菌来开发抗癌药物的研究策略。我们还提出了一种将新型细菌抗癌药物与辐射相结合的开发策略。通过修饰先前开发的抗辐射基因INHA的miRNA表达载体，产生了表达miRNA的菌株。利用皮肤癌细胞系证实了INHA的抗癌作用。我们还测试了一种包含细菌和辐射的联合策略，以评估其对耐辐射小鼠黑色素瘤的抗癌疗效，作为一种新策略来提高放射治疗的效果。重组菌株即使与放射治疗联合使用时也能促进有效的细胞死亡，放射治疗通过增强活性氧的产生发挥其细胞毒性作用。此外，细菌疗法与放射疗法的联合提高了放射治疗的疗效。当与放射治疗联合使用时，即使施用于患有耐辐射肿瘤的动物，细菌疗法也表现出有效的抗癌特性。这种策略可能会促进细胞中细胞因子的分泌，并更有效地减少动物体内残留的细菌数量。因此，本研究可能会促成一种策略的开发，即利用表达癌症特异性miRNA来提高对诸如耐辐射等难治性癌症的放射治疗效果。
