Law Betty Yuen Kwan, Qu Yuan Qing, Mok Simon Wing Fai, Liu Hauwei, Zeng Wu, Han Yu, Gordillo-Martinez Flora, Chan Wai-Kit, Wong Keith Man-Chung, Wong Vincent Kam Wai
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, P.R. China.
Department of Chemistry, South University of Science and Technology of China, Tangchang Boulevard, Nanshan District, Shenzhen, P.R. China.
Oncotarget. 2017 Jul 5;8(33):55003-55021. doi: 10.18632/oncotarget.18991. eCollection 2017 Aug 15.
Platinating compounds including cisplatin, carboplatin, and oxaliplatin are common chemotherapeutic agents, however, patients developed resistance to these clinical agents after initial therapeutic treatments. Therefore, different approaches have been applied to identify novel therapeutic agents, molecular mechanisms, and targets for overcoming drug resistance. In this study, we have identified a panel of cobalt complexes that were able to specifically induce collateral sensitivity in taxol-resistant and p53-deficient cancer cells. Consistently, our reported anti-cancer functions of cobalt complexes 1-6 towards multidrug-resistant cancers have suggested the protective and non-toxic properties of cobalt metal-ions based compounds in anti-cancer therapies. As demonstrated in xenograft mouse model, our results also confirmed the identified cobalt complex 2 was able to suppress tumor growth . The anti-cancer effect of the cobalt complex 2 was further demonstrated to be exerted via the induction of autophagy, cell cycle arrest, and inhibition of cell invasion and P-glycoprotein (P-gp) activity. These data have provided alternative metal ion compounds for targeting drug resistance cancers in chemotherapies.
包括顺铂、卡铂和奥沙利铂在内的铂类化合物是常见的化疗药物，然而，患者在初始治疗后会对这些临床药物产生耐药性。因此，人们采用了不同的方法来确定新型治疗药物、分子机制以及克服耐药性的靶点。在本研究中，我们鉴定出一组钴配合物，它们能够在耐紫杉醇和p53缺陷的癌细胞中特异性诱导旁敏感性。一致地，我们报道的钴配合物1 - 6对多药耐药癌症的抗癌功能表明，基于钴金属离子的化合物在抗癌治疗中具有保护和无毒的特性。正如在异种移植小鼠模型中所证明的，我们的结果还证实了所鉴定的钴配合物2能够抑制肿瘤生长。钴配合物2的抗癌作用进一步证明是通过诱导自噬、细胞周期阻滞以及抑制细胞侵袭和P -糖蛋白（P - gp）活性来实现的。这些数据为化疗中针对耐药癌症提供了替代的金属离子化合物。
