Livin enhances chemoresistance in head and neck squamous cell carcinoma

Abstract

The responsiveness of head and neck squamous cell carcinoma (HNSCC) to chemotherapy widely affects prognosis. Overcoming chemoresistance is necessary to improve prognoses in patients with advanced HNSCC. Evasion of apoptosis by cancer cells is a major cause of chemoresistance. Livin, a member of the human inhibitors of apoptosis protein family, is highly expressed in various human cancer tissues and is associated with tumor progression and poor prognosis in human cancers. The aim of the present study was to evaluate the role of Livin in the susceptibility to popularly used chemotherapeutic drugs such as cisplatin, 5-fluorouracil (FU) and docetaxel in human HNSCC cell lines (SNU1041, PCI1 and PCI50 cells). Reverse transcription polymerase chain reaction and western blotting were performed to determine mRNA and protein expression levels. Cell viability and apoptosis assays were used to assess the functional effects of small-interfering RNA-mediated knockdown of Livin. Each HNSCC cell line had different sensitivity to chemotherapeutic drugs. Livin knockdown significantly enhanced cytotoxicity to cisplatin, 5-FU and docetaxel in human HNSCC cells. Livin knockdown induced apoptosis and enhanced chemotherapyinduced apoptosis to cisplatin, 5-FU and docetaxel. Consistent with this, Livin-knockdown cells showed greater expression of cleaved caspases-3 and -7 and poly(ADP-ribose)polymerase compared with that in control cells after cisplatin, 5-FU, or docetaxel treatment. In conclusion, our results suggest that siRNA-mediated Livin knockdown enhanced the chemosensitivity of the three HNSCC cell lines to cisplatin, 5-FU and docetaxel. Although further investigations are required to support these findings, our results demonstrated that novel therapeutic strategies with combined use of siRNA targeting Livin and chemotherapeutic agents may have applications in the treatment of advanced HNSCC.