Head and Neck Surgery, the Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, PR China.
Oral and Maxillofacial Surgery, the Stomatology Hospital, Zhejiang University School of Medicine, No.166 Qiutao Road, Hangzhou, 310016, Zhejiang, PR China.
BMC Oral Health. 2024 Aug 6;24(1):898. doi: 10.1186/s12903-024-04459-4.
Human epidermal growth factor receptor 2 (HER2) plays an important role in the progression of multiple solid tumors and induces resistance to epidermal growth factor receptor (EGFR) target treatment. However, the expression status and the clinical significance of HER2 in oral squamous cell carcinoma (OSCC) is still controversial. Pyrotinib (PYR) is a promising novel EGFR/HER2 dual inhibitor, whose efficacy in OSCC has not been determined.
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.
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.
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.
人表皮生长因子受体 2（HER2）在多种实体肿瘤的进展中发挥重要作用，并诱导对表皮生长因子受体（EGFR）靶向治疗的耐药性。然而，HER2在口腔鳞状细胞癌（OSCC）中的表达状态和临床意义仍存在争议。吡咯替尼（PYR）是一种有前途的新型 EGFR/HER2 双重抑制剂，其在 OSCC 中的疗效尚未确定。
本研究通过组织微阵列分析（TMA），对 57 例局部晚期初治 OSCC 患者进行了研究，以探讨 HER2 表达水平与预后的关系。通过体外和体内实验研究了 PYR 在 OSCC 中的疗效。在 OSCC 细胞系和异种移植瘤中，通过 Western blot 评估 HER2 的主要下游信号通路，以探讨 PYR 的潜在作用机制。
本研究表明 OSCC 的原发肿瘤具有更高的 HER2 表达水平。HER2 过表达的患者总生存期较差（P<0.014），无病生存期较差（P<0.042）。体外实验表明，PYR 抑制了 OSCC 细胞的增殖、集落形成和迁移。它还促进了 OSCC 细胞的凋亡，并诱导了细胞周期停滞。此外，PYR 能够有效地抑制 OSCC 的发生和发展。Western blot 显示 PYR 通过抑制 HER2、AKT 和 ERK 的磷酸化来抑制 OSCC。
本研究在体外和体内展示了 PYR 对 OSCC 的抗作用，并证明 PYR 通过诱导凋亡抑制 OSCC 细胞，其作用机制涉及 HER2/AKT 和 ERK 通路。本研究结果还表明，局部晚期 OSCC 患者可能受益于 HER2 检测和 EGFR/HER2 双重抑制治疗。
