Many cases of cancer recurrence occur because some cancer cells acquire drug resistance and proliferate. This represents one of the major problems for cancer treatment. Acquisition of drug resistance in cancer cells has been investigated in many previous studies, but drug resistance has not yet been overcome, because resistant cells express a variety of proteins that contribute to drug resistance. Proteome analysis allows the comprehensive measurement of the expression of many proteins and identifies proteins that contribute to drug resistance. Additionally, phosphoproteome analysis can reveal signaling pathways involved in drug resistance. However, previous studies have focused on only one time point. The dynamic changes that occur after drug treatment in drug resistant cancer cells remain unknown. Here we compared the differential cellular responses to cisplatin in ovarian cancer cell lines that were drug sensitive (A2780) and resistant (A2780cis) to cisplatin, using temporal proteome and phosphoproteome analysis. By analyzing temporal data, the differential DNA damage and cell cycle responses to cisplatin in A2780 and A2780cis were highlighted, and A2780cis exhibited various drug resistance mechanisms to escape the effects of cisplatin. Additionally, we detected differences in the expression and phosphorylation of proteins that were not previously known to be involved in cisplatin resistance. From these proteins, we confirmed mRNA expression of FABP5, NOLC1, PHGDH, SDHA, and 14-3-3 sigma. In this study, we estimated the contribution of these proteins to drug resistance for applying cancer treatment.
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