title: 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.
authors.affiliation: Central Laboratory and Radiation Biology, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Adachi
authors.forename: Kei
authors.initials: K
authors.lastname: Ijichi
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ogawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yasui
authors.forename: Masakazu
authors.initials: M
authors.lastname: Fukushima
authors.forename: Kanji
authors.initials: K
authors.lastname: Ishizaki