Hypersensitivity to cisplatin after hRev3 mRNA knockdown in head and neck squamous cell carcinoma cells

Abstract

Resistance to platinum-based chemotherapy frequently poses a significant problem in the treatment of head and neck squamous cell carcinomas (HNSCCs). In this study, we isolated cisplatin-resistant UM-SCC-23 CDDP/R cells from a UM-SCC-23 head and neck squamous cell carcinoma cell line. The UM-SCC-23 CDDP/R cells were approximately 3.5-fold more resistant to cisplatin than the UM-SCC-23 cells. Translesion DNA synthesis (TLS) is one of the major pathways involved in post-replication repair. To ascertain whether TLS is involved in cisplatin resistance in human cancer cells, we analyzed expression of the Rev3 gene, which encodes the catalytic subunit of DNA polymerase ζ (Polζ), using quantitative PCR. Expression of hRev3 mRNA in the UM-SCC-23 CDDP/R cells was approximately 1.4-fold higher than in the UM-SCC-23 cells. In both types of cells, expression of hRev3 mRNA was suppressed using siRNAs. Cisplatin sensitivity after hRev3 mRNA knockdown increased approximately 2-fold in UM-SCC-23 cells and approximately 3-fold in UM-SCC-23 CDDP/R cells. This study suggests that hRev3 knockdown with siRNAs increases sensitivity to cisplatin. Inhibition of the hRev3 gene may therefore prove to be a novel clinical strategy for reducing resistance to platinum-based chemotherapy in HNSCC.