Anais dos Simpósios de Oncobiologia
XIV Oncobiology Symposium

INTRODUCTION AND OBJECTIVES: Osteopontin (OPN) is overexpressed in several tumor types and has been correlated to chemoresistance. However, the contribution of OPN splicing isoforms (OPN-SI) in chemoresistance needs further investigation. Here, we aimed to evaluate the expression patterns of each tested OPN-SI in ovarian carcinoma cell lines resistant to cisplatin (CDDP), and mainly OPNc role on drug resistance. MATERIAL AND METHODS: We tested ACRP ovarian cancer cells resistant to CDDP, as well as its parental cell line, A2780. Some data obtained using the ACRP cell line have been also validated by testing an ovarian cancer cell line resistant to doxorrubicin (DOX), named OVCar-8/DoxR, which was originated from OVCar-8 cells. The analysis of transcriptional expression of OPN-SI, epithelial-mesenchymal transition (EMT) markers, as well as EMT-related cytokines has been performed using quantitative real-time PCR (RT-qPCR). OPNc was silenced in ACRP and OVCar-8/DoxR cells lines using anti-OPNc DNA oligomers, while stably overexpressed in A2780 cells. Functional assays have been performed using cell growth, viability and colony formation assays. RESULTS AND CONCLUSION: We found that among the three tested OPN-SI, OPNc was the most overexpressed transcript in ACRP and OVCar-8/DoxR resistant cells. Likewise, P-glycoprotein multidrug transporter (P-gp) was overexpressed in both drug resistant ovarian cancer cell lines. OPNc knockdown sensitized ACRP cells to CDDP treatment, besides downregulating P-gp expression. Also, it impaired cell growth and colony formation, besides reversing the expression of EMT markers and EMT-related cytokines. Interestingly, although OPNc stable overexpression conferred an improved proliferative advantage to A2780 cells, it notably increased sensitivity to CDDP. These results suggest that OPNc silencing might represent a putative approach to further sensitize ovarian cancer resistant cells to chemotherapeutic agents.