Molecular investigation of drug resistance mechanism in human ovarian cancer.

摘要

Drug resistance is the major barrier to successful cancer chemotherapy. Understanding the mechanisms involved will help design strategies to enhance chemosensitivity in the drug resistant cancers. The major objective of this study is to explore the cellular signaling pathways in human ovarian cancer cell lines and to investigate mechanisms by which human ovarian cancer cells develop drug resistance after cisplatin treatment. In contrast to conventional approaches, we performed a top-down approach where the sophisticated designed RepairChip platform was employed to explore global signaling events in the samples. Quantitative analysis and intuitive display of DNA repair related biological information in the context of the RepairNet database were then performed. Candidate genes discovered that were potentially associated with cisplatin resistance in ovarian cancer, were verified via real time PCR. The expression patterns of these genes at the protein level were confirmed by immunoblotting assays. Further investigation can be carried out to characterize how quantitative changes in the flow of signals can control the cellular processes.