Background: CIGB-300 is a pro-apoptotic peptide that abrogates CK2-mediated phosphorylation, and can elicit synergistic interaction in vitro and in vivo when combined with certain anticancer drugs.

Objective: The combination of CIGB-300 with cisplatin is studied through data mining and expressionbased proteomics to reveal the molecular basis of this interaction. Cisplatin resistance-associated proteins, which have also been reported as CK2 substrates, were first identified by bioinformatic analyses.

Methods: Data from these analyses suggested that the cisplatin resistance phenotype could be directly improved by inhibiting CK2 phosphorylation on specific substrates. Furthermore, 157 proteins were differentially modulated on the NCI-H125 lung cancer cell line in response to CIGB-300, cisplatin or both drugs as determined by LC-MS/MS.

Results: The expression of 28 cisplatin resistance-associated proteins was changed when cisplatin was combined with CIGB-300. Overall, the proteins identified are also related to cell survival, cell proliferation and metastasis. Furthermore, the CIGB-300 regulated proteome revealed proteins that were initially involved in the mechanism of action of CIGB-300 and cisplatin as single agents.

Conclusion: This is the first report describing the protein array modulated by combining CIGB-300 and cisplatin that will support the rationale for future clinical settings based on a multi-target cancer therapy.

背景：CIGB-300是一种促凋亡肽，可消除CK2介导的磷酸化，并与某些抗癌药物联合使用时可在体内外引起协同作用。

目的：通过数据挖掘和基于表达的蛋白质组学研究CIGB-300与顺铂的组合，以揭示这种相互作用的分子基础。顺铂耐药相关蛋白（也已报道为CK2底物）首先通过生物信息学分析鉴定。

方法：这些分析的数据表明，可以通过抑制特定底物上的CK2磷酸化来直接改善顺铂耐药性表型。此外，通过LC-MS / MS测定，响应CIGB-300，顺铂或两种药物，在NCI-H125肺癌细胞系上对157种蛋白质进行了差异调节。

结果：当顺铂与CIGB-300联合使用时，改变了28种顺铂耐药相关蛋白的表达。总的来说，鉴定出的蛋白质也与细胞存活，细胞增殖和转移有关。此外，CIGB-300调节的蛋白质组揭示了最初作为单一药剂参与CIGB-300和顺铂作用机制的蛋白质。

结论：这是第一份描述结合CIGB-300和顺铂调节的蛋白阵列的报告，该蛋白阵列将为基于多靶点癌症疗法的未来临床环境提供理论依据。