School of Medicine, Jianghan University, Wuhan, Hubei 430056, P.R. China.
Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, Hubei 430056, P.R. China.
Oncol Rep. 2023 Sep;50(3). doi: 10.3892/or.2023.8607. Epub 2023 Jul 28.
Oxaliplatin (Oxa) is one of the most effective chemotherapeutic drugs used in the treatment of colorectal cancer (CRC). However, the use of this drug is associated with severe side‑effects and patients eventually develop resistance to Oxa. In recent years, copper complexes have been extensively investigated as substitutes for platinum‑based drugs. Therefore, a number of copper complexes have also been developed for cancer therapy, such as copper (II) complex of salicylate phenanthroline [Cu(sal)(phen)]. In the present study, the antitumor activity and the related molecular mechanisms of Cu(sal)(phen) were examined in CRC cells. As compared with the chemotherapeutic drug, Oxa, Cu(sal)(phen) was more effective in inducing apoptosis and reactive oxygen species (ROS) production, and in decreasing mitochondrial membrane potential in the CRC cell lines, HCT116 and SW480. In addition, the expression of the apoptosis‑related proteins, Bcl‑2 and survivin, and those of the upstream regulators, p‑JAK2 and p‑STAT5, were significantly decreased in the two cell lines following treatment with Cu(sal)(phen). Furthermore, the efficacy of the complex against CRC was found to be excellent in an animal model. The results of immunohistochemical analysis revealed that the expression levels of Bcl‑2, survivin and Ki‑67 in tumor tissues were decreased following Cu(sal)(phen) treatment. The antitumor mechanisms underlying Cu(Sal)(phen) treatment were the induction of ROS generation, the inhibition of the JAK2/STAT5 signaling pathway and the downregulation of the expression of anti‑apoptotic proteins, such as Bcl‑2 and survivin. On the whole, the findings of the present study indicated that Cu(sal)(phen) effectively inhibited the viability and proliferation of HCT116 and SW480 CRC cells; in the future, the authors aim to conduct further experiments in future studies to provide more evidence that supports the development of Cu(sal)(phen) as a therapeutic agent for CRC.
奥沙利铂（Oxa）是治疗结直肠癌（CRC）最有效的化疗药物之一。然而，这种药物的使用与严重的副作用有关，并且患者最终会对 Oxa 产生耐药性。近年来，铜配合物已被广泛研究作为铂类药物的替代品。因此，已经开发出许多用于癌症治疗的铜配合物，例如水杨酸邻菲咯啉[Cu（sal）（phen）]的铜（II）配合物。在本研究中，研究了 Cu（sal）（phen）在 CRC 细胞中的抗肿瘤活性及其相关分子机制。与化疗药物奥沙利铂相比，Cu（sal）（phen）在诱导 CRC 细胞系 HCT116 和 SW480 细胞凋亡和活性氧（ROS）产生以及降低线粒体膜电位方面更有效。此外，在用 Cu（sal）（phen）处理后，两种细胞系中凋亡相关蛋白 Bcl-2 和 survivin 以及上游调节剂 p-JAK2 和 p-STAT5 的表达均显著降低。此外，该复合物在动物模型中对 CRC 的疗效非常好。免疫组织化学分析的结果表明，在用 Cu（sal）（phen）处理后，肿瘤组织中 Bcl-2、survivin 和 Ki-67 的表达水平降低。Cu（Sal）（phen）治疗的抗肿瘤机制是诱导 ROS 生成、抑制 JAK2/STAT5 信号通路以及下调抗凋亡蛋白如 Bcl-2 和 survivin 的表达。总的来说，本研究的结果表明，Cu（sal）（phen）有效抑制了 HCT116 和 SW480 CRC 细胞的活力和增殖；在未来，作者旨在进一步开展未来研究的实验，为 Cu（sal）（phen）作为 CRC 治疗剂的开发提供更多证据支持。
