Department of Urology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
Biomed Res Int. 2017;2017:8050313. doi: 10.1155/2017/8050313. Epub 2017 Oct 15.
The development of multitargeting drugs is an emerging trend in cancer research. To promote further development and clinical application of multitargeting drugs, this research was performed. MTT assay and flow cytometry of Annexin V/propidium iodide staining were used to confirm the proapoptotic efficacy of a novel combi-targeting molecule, JDF12, against DU145 prostate cancer (PCa) cells. Differentially expressed proteins between control and JDF12-treated cultures were revealed by isobaric tags for relative and absolute quantitation (iTRAQ), and part of them was confirmed by quantitative PCR. Differentially expressed proteins were further analyzed for function, pathway association, and protein-protein interactions using GO, KEGG, and STRING databases. A total of 119 differentially expressed proteins, 70 upregulated and 49 downregulated, were implicated in the anticancer effects of JDF12. Many of these proteins are involved in biosynthesis, response to stress, energy metabolism, and signal transduction. This study provides important information for understanding the anti-PCa mechanisms of JDF12, and well-designed combi-targeting drugs may possess stronger anticancer efficacy than single-targeting drugs and are thus promising candidates for clinical application.
多靶点药物的开发是癌症研究中的一个新兴趋势。为了促进多靶点药物的进一步发展和临床应用，进行了这项研究。MTT 检测和 Annexin V/碘化丙啶染色的流式细胞术用于证实新型组合靶向分子 JDF12 对 DU145 前列腺癌细胞（PCa）的促凋亡作用。通过等重同位素标记相对和绝对定量（iTRAQ）揭示了对照和 JDF12 处理培养物之间的差异表达蛋白，其中一部分通过定量 PCR 进行了确认。通过 GO、KEGG 和 STRING 数据库进一步分析差异表达蛋白的功能、通路关联和蛋白质-蛋白质相互作用。JDF12 的抗癌作用涉及到总共 119 个差异表达蛋白，其中 70 个上调，49 个下调。这些蛋白中的许多参与生物合成、应激反应、能量代谢和信号转导。这项研究为理解 JDF12 的抗 PCa 机制提供了重要信息，精心设计的组合靶向药物可能比单靶点药物具有更强的抗癌疗效，因此是临床应用的有前途的候选药物。
