Pegylated liposomal doxorubicin/oxaliplatin chemotherapy can overcome cisplatin resistance in spectrin αII-overexpressing ovarian carcinoma

Abstract

Background: Spectrin αII contributes to cisplatin and carboplatin resistance in ovarian serous carcinoma cells, and its expression in surgical specimens is a valid predictor of prognosis. We sought to identify effective drugs for spectrin αII-mediated cisplatin-resistant cells. Materials and Methods: We employed SKOV3 cells with small interfering RNA-mediated spectrin αII downregulation, serous carcinoma cells (NOS2), cisplatin-resistant cells (NOS2CR2), and oxaliplatin-resistant cells (NOS2OXR). Results: In the drug-sensitivity test, oxaliplatin was not affected by the inhibition of spectrin αII expression and was effective for cisplatin-resistant NOS2CR2 cells. NOS2OXR cells did not express higher levels of spectrin αII compared to NOS2 in western blot analysis. Six non-platinum anticancer drugs were not affected by the inhibition and was effective for resistant NOS2CR2 and NOS2OXR cells. Doxorubicin exhibited potent cytotoxicity at 2 μM against both resistant cell lines. Conclusion: Pegylated liposomal doxorubicin/oxaliplatin regimen may be effective for cisplatin-resistant ovarian carcinoma with spectrin αIIoverexpression.