Abstract
The major problems faced during the treatment of ovarian cancer are metastasis and the development of intrinsic or acquired drug resistance. The present study assessed whether tumor protein p53 binding protein 1 (53BP1) regulated migration and modulated chemotherapy resistance in SKOV3 cells and identified proteins associated with the molecular mechanisms underlying this coordinate regulation. SKOV3 cells were transfected using a 53BP1-expressing vector, which induced 53BP1 overexpression. The migration of the transfected cells was observed using a Transwell assay. The expression of matrix metalloproteinase (MMP)-2 and MMP-9 were assayed using gelatin zymography. In addition, the effects of 53BP1 on the chemosensitivity of SKOV3 cells to cisplatin were evaluated using MTT and western blot assays. Compared with the control, the average number of migrating SKOV3/pLPC-53BP1 cells was decreased from 230±58 to 45±12 (P<0.05) and the protein expression of MMP-9 was significantly inhibited. However, the chemosensitivity of SKOV3/pLPC-53BP1 to cisplatin decreased significantly: Cisplatin half maximal inhibitory concentration (IC50) for SKOV3/pLPC-53BP1=7.58±0.51 µg/ml; cisplatin IC50 for control=2.98±0.27 µg/ml (P<0.01). Decreased chemosensitivity to cisplatin may be associated with increased expression of phosphorylated-protein kinase B and cyclin dependent kinase 2 and with decreased expression of p21 and the B cell lymphoma (Bcl)-2 associated X/Bcl-2 ratio. The results of the present study demonstrated that 53BP1 may inhibit migration but upregulate chemoresistance to cisplatin in SKOV3 cells.