Yoon Tae Mi, Kim Sun-Ae, Lee Dong Hoon, Lee Joon Kyoo, Park Young-Lan, Lee Kyung-Hwa, Chung Ik-Joo, Joo Young-Eun, Lim Sang Chul
Department of Otorhinolaryngology-Head and Neck Surgery, Chonnam National University Medical School, Gwanju 501-757, Republic of Korea.
Department of Internal Medicine, Chonnam National University Medical School, Gwanju 501-757, Republic of Korea.
Oncol Rep. 2017 Jun;37(6):3667-3673. doi: 10.3892/or.2017.5584. Epub 2017 Apr 19.
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 chemotherapy-induced 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.
头颈部鳞状细胞癌（HNSCC）对化疗的反应性广泛影响预后。克服化疗耐药性对于改善晚期HNSCC患者的预后至关重要。癌细胞逃避凋亡是化疗耐药的主要原因。Livin是人类凋亡抑制蛋白家族的成员，在各种人类癌症组织中高表达，与人类癌症的肿瘤进展和不良预后相关。本研究的目的是评估Livin在人HNSCC细胞系（SNU1041、PCI1和PCI50细胞）对常用化疗药物如顺铂、5-氟尿嘧啶（FU）和多西他赛的敏感性中的作用。进行逆转录聚合酶链反应和蛋白质印迹以确定mRNA和蛋白质表达水平。使用细胞活力和凋亡测定来评估小干扰RNA介导的Livin敲低的功能作用。每种HNSCC细胞系对化疗药物具有不同的敏感性。Livin敲低显著增强了人HNSCC细胞对顺铂、5-FU和多西他赛的细胞毒性。Livin敲低诱导凋亡并增强了对顺铂、5-FU和多西他赛的化疗诱导凋亡。与此一致，与顺铂、5-FU或多西他赛处理后的对照细胞相比，Livin敲低细胞显示出更高水平的裂解的半胱天冬酶-3和-7以及聚（ADP-核糖）聚合酶的表达。总之，我们的结果表明，siRNA介导的Livin敲低增强了三种HNSCC细胞系对顺铂、5-FU和多西他赛的化学敏感性。尽管需要进一步研究来支持这些发现，但我们的结果表明，联合使用靶向Livin的siRNA和化疗药物的新型治疗策略可能在晚期HNSCC的治疗中具有应用价值。
