Zhou Jing, Zhao Rongce, Zhou Haoxuan, Yang Shuping, Tao Feiyan, Xie Yongmei, Wang Hongli, Yun Jingping
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China.
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guang Zhou, China.
Front Pharmacol. 2023 May 23;14:1196158. doi: 10.3389/fphar.2023.1196158. eCollection 2023.
Colorectal cancer (CRC) is one of the most common malignancies causing the third highest mortality rate in the world. It is particularly urgent to explore effective therapeutic strategies to overcome this disease. We identified a novel benzothiazole derivative (BTD) that may serve as a potentially effective agent against CRC. MTT assays, cell colony formation assays, EdU staining assays, flow cytometry, RNA-seq, Western blotting, and migration and invasion assays were used to examine the effects of BTD on cell proliferation, apoptosis, metastasis, and the cell cycle. The antitumor activity of BTD was investigated in a CT26 tumor-bearing mouse model. Immunohistochemistry (IHC) was performed to examine the protein expression in mouse tumors. Hematology, biochemical analysis, and H&E staining were used to assess the biosafety of BTD. We observed that BTD suppressed cell proliferation and metastasis and promoted the apoptosis of tumor cells . Treatment with BTD at a tolerable dose significantly reduced tumor growth in CT26-tumor-bearing mice and appeared to be safe. Treatment of BTD induced apoptosis by increasing the generation of reactive oxygen species (ROS) and evoking the loss of mitochondrial transmembrane potential. Overall, BTD suppressed cell proliferation and metastasis, and induced apoptosis of colorectal tumor cells through the ROS-mitochondria-mediated apoptotic pathway. The preliminary proof of the antitumor activity and relative safety of BTD were validated in a mouse model. Our findings suggest that BTD could serve as a potentially safe and effective candidate for CRC treatment.
结直肠癌（CRC）是世界上最常见的恶性肿瘤之一，死亡率位居第三。探索有效的治疗策略来攻克这种疾病尤为迫切。我们鉴定出一种新型苯并噻唑衍生物（BTD），它可能是一种潜在有效的抗结直肠癌药物。采用MTT法、细胞集落形成试验、EdU染色试验、流式细胞术、RNA测序、蛋白质印迹法以及迁移和侵袭试验来检测BTD对细胞增殖、凋亡、转移和细胞周期的影响。在CT26荷瘤小鼠模型中研究了BTD的抗肿瘤活性。通过免疫组织化学（IHC）检测小鼠肿瘤中的蛋白表达。利用血液学、生化分析和苏木精-伊红（H&E）染色来评估BTD的生物安全性。我们观察到BTD抑制细胞增殖和转移，并促进肿瘤细胞凋亡。以可耐受剂量的BTD治疗可显著降低CT26荷瘤小鼠的肿瘤生长，且似乎是安全的。BTD治疗通过增加活性氧（ROS）的生成和引发线粒体跨膜电位的丧失来诱导凋亡。总体而言，BTD通过ROS-线粒体介导的凋亡途径抑制细胞增殖和转移，并诱导结直肠肿瘤细胞凋亡。BTD抗肿瘤活性和相对安全性的初步证据在小鼠模型中得到了验证。我们的研究结果表明，BTD可能是一种潜在安全有效的结直肠癌治疗候选药物。
