铂类药物由于其独特的作用机制而发挥抗肿瘤活性，但毒副反应和耐药性使其临床应用受限。抑制耐药的抗肿瘤药物和铂类药物通过化学键合而成的四价铂复合物由于毒性较低，耐药程度低成为一种新的联用方式，是目前肿瘤研究热点。CK2是一类重要的肿瘤靶分子，研究表明其能诱导DNA损伤修复，从而引发肿瘤细胞耐药。我们将CK2抑制剂CX-4945轴向引入顺铂中，形成新型四价铂复合物Cx-platin。前期研究表明Cx-platin具有较好的抗肿瘤活性，对肿瘤耐药细胞较顺铂敏感，但其分子机制并不明确。本课题应用HPLC、ICP-MS、分子细胞生物学等方法，研究Cx-platin降低肿瘤耐药性的作用机制，寻找可能靶点。利用体内外耐药模型深入研究其在诱导细胞凋亡和DNA损伤方面的分子机制，综合评价Cx-platin的体内外抗肿瘤活性，为新型四价铂复合物Cx-platin的临床应用提供理论基础。

As one of the most important chemotherapy drugs with unique anticancer mechanism, platinum-base cancer treatments have been commonly used but greatly limited in clinical application by their toxic effect and drug resistance. Drug combination therapies are originally devised to decrease the incidence of drug resistance. Among them, a fusion of targeting antitumor drugs and platinum plays an important role in the drug combination therapies. We have identified protein kinase CK2, a promising therapeutic target in oncology, regulates DNA damage repair, which can induce drug resistance. Cx-platin, a fusion of CX-4945 and cisplatin, exhibits significant cytotoxicity in CK2-overexpressed tumor cells and overcome the drug resistance of cisplatin-resistant cells. However, the mechanisms underlying the synergistic antitumor responses are still unclear. Based on the complexation of CX-4945 and Cisplatin, the mechanistic investigation was carried out on the unique mode of action and the decrease of cisplatin resistance. In vivo and in vitro cisplatin-resistant models were used to understand its detailed mechanism, which aim to support the evaluation of the clinical setting and drug development of Cx-platin.