METHODS: 57 locally advanced de novo OSCC patients were included in this study to investigate the relationship between the HER2 expression levels and the prognosis by the tissue microarray analysis (TMA). In vitro and in vivo experiments were performed to retrieve the efficacy of PYR in OSCC. The main downstream of HER2 was evaluated by western blotting in OSCC cell lines and xenograft tumors to explore the potential mechanism of PYR.
RESULTS: This study revealed the primary tumor of OSCC had higher HER2 expression levels. Patients with HER2 overexpression had poor overall survival (P < 0.014) and poor disease free survival (P < 0.042). In vitro, PYR suppressed the proliferation, colony formation and migration of OSCC cells. It also promoted apoptosis of OSCC cells and induced cell cycle arrest. Furthermore, PYR was able to inhibit the occurrence and development of OSCC effectively in vivo. Western blotting revealed that PYR suppressed OSCC by inhibiting the phosphorylation of HER2, AKT and ERK.
CONCLUSIONS: This study exhibited the anti-OSCC effects of PYR in vitro and in vivo, and demonstrated PYR inhibited OSCC cells by inducing apoptosis via the HER2/ AKT and ERK pathway. The result of this study also indicated locally advanced OSCC patients might benefit from HER2 assay and EGFR/HER2 dual inhibit treatment.
方法:本研究纳入57例局部晚期新生OSCC患者,通过组织微阵列分析(TMA)研究HER2表达水平与预后之间的关系。进行体外和体内实验以检索PYR在OSCC中的功效。通过蛋白质印迹法对OSCC细胞系和异种移植肿瘤中HER2的主要下游进行评估,以探讨PYR的潜在机制。
结果:本研究显示OSCC原发肿瘤有较高的HER2表达水平。HER2过表达患者的总生存期(P<0.014)和无病生存期(P<0.042)均较差。体外,PYR抑制了增殖,OSCC细胞的集落形成和迁移。它还促进OSCC细胞的凋亡并诱导细胞周期停滞。此外,PYR能够在体内有效抑制OSCC的发生和发展。Western印迹显示PYR通过抑制HER2、AKT和ERK的磷酸化来抑制OSCC。
结论:本研究显示了PYR在体外和体内的抗OSCC作用,并证明PYR通过HER2/AKT和ERK途径诱导凋亡抑制OSCC细胞。这项研究的结果还表明局部晚期OSCC患者可能受益于HER2测定和EGFR/HER2双重抑制治疗。