Hassanpour Khodaei Sepideh, Sabetkam Shahnaz, Mazloumi Zeinab, Dizaji Asl Khadijeh, Rafat Ali
Department of Dentistry, Eastern Mediterranean University (EMU), Mersin 10, Famagusta, North Cyprus, Turkey.
Department of Anatomy, Faculty of Medicine, University of Kyrenia, Kyrenia, Northern Cyprus, Turkey.
Mutat Res. 2025 Jan-Jun;830:111905. doi: 10.1016/j.mrfmmm.2025.111905. Epub 2025 Apr 11.
Colorectal cancer (CRC) is the third most common cancer worldwide and causes more than 50,000 deaths in the United States each year. Due to the limited therapeutic options and poor prognosis in CRC, extensive research and development of novel therapeutic methods is essential. In this regard, the presence of cancer stem cells with unlimited division ability is the main reason for the therapeutic resistance in CRC. Tigecycline is a pharmacological mitochondria inhibitor and blocks mitochondria-related cell proliferation in cancer cells. This study investigated the effects of Tigecycline combined with radiotherapy on CRC cell apoptosis.
Human colorectal cancer cells (HCT-116) were treated with Tigecycline, and cell viability was measured with MTT assay. In the next step, the cells were exposed to radiation using a Siemens Primus 6 MV linear accelerator at radiation dose of 400 cGy. Finally, we evaluated cancer cell apoptosis, caspase-3 activity and apoptotic-related genes expression with AnnexinV/PI, flowcytometry and gene expression, respectively.
The MTT assay revealed an IC50 value of 93 μM for Tigecycline after 48 hours. Mitochondria inhibition, at its IC50 value, sensitizes colorectal cancer cells to radiotherapy. Compared to monotherapy, the combination therapy increased the number of apoptotic cells and caspase-3 activity, up-regulated pro-apoptotic genes, and down-regulated anti-apoptotic genes.
In conclusion, our data suggests that targeting mitochondria may represent a clinically relevant approach to enhance the sensitivity of colorectal cancer cells to therapy. These findings could provide new insights into cancer therapy and might be used as a novel method to improve the current state of CRC therapy.
结直肠癌（CRC）是全球第三大常见癌症，在美国每年导致超过50000人死亡。由于结直肠癌的治疗选择有限且预后较差，广泛开展新型治疗方法的研发至关重要。在这方面，具有无限分裂能力的癌症干细胞的存在是结直肠癌治疗耐药的主要原因。替加环素是一种药理学线粒体抑制剂，可阻断癌细胞中与线粒体相关的细胞增殖。本研究调查了替加环素联合放疗对结直肠癌细胞凋亡的影响。
用人结直肠癌细胞（HCT-116）进行替加环素处理，并用MTT法测定细胞活力。下一步，使用西门子Primus 6 MV直线加速器以400 cGy的辐射剂量对细胞进行照射。最后，我们分别用AnnexinV/PI、流式细胞术和基因表达评估癌细胞凋亡、半胱天冬酶-3活性和凋亡相关基因的表达。
MTT法显示替加环素在48小时后的IC50值为93μM。在其IC50值时，线粒体抑制使结直肠癌细胞对放疗敏感。与单一疗法相比，联合疗法增加了凋亡细胞数量和半胱天冬酶-3活性，上调了促凋亡基因，下调了抗凋亡基因。
总之，我们的数据表明，靶向线粒体可能是一种提高结直肠癌细胞对治疗敏感性的临床相关方法。这些发现可为癌症治疗提供新的见解，并可能用作改善当前结直肠癌治疗状况的新方法。
