Pituitary adenomas (PAs) hypersecrete hormones or cause mass effect symptoms, with 10%–35% patients showing resistance to standard therapies. Targeting epidermal growth factor receptor (EGFR) has significantly improved the clinical outcome in many cancers. In this study, immunochemistry results showed that EGFR associated H-scores in 116 PA samples were higher than those in pituitary glands, and that p21, p27-and Wif-1 associated H-scores were lower (P < 0.05 for all). Patients with high levels of EGFR had increased PA invasion, lower total resection, and lower p21 and p27 expression than those with low levels of EGFR expression. Dual-luciferase reporter gene assays showed that EGFR was the target gene of miR-137, and miR-137 mimic could inhibit the cell proliferation of GH3 cells and induce apoptosis and G1-phase arrest of GH3 cells. A combination of miR-137 mimic and AZD9291 had stronger inhibition on GH3 cells compared with miR-137 mimic or AZD9291 alone; furthermore, miR-137 inhibitor partially reversed the inhibition of AZD9291. p21 and p27 were shown to be involved in the miR-137- and AZD9291-mediated effects on GH3 cells. In all, activation of EGFR in PAs was related to tumor invasive behavior, which reduced the total resection of PAs in patients. A combination of miR-137 and AZD9291 provided a potential treatment for PAs, especially for patients who show resistance to standard treatment.

垂体腺瘤 (PA) 分泌过多激素或引起占位效应症状，10%–35% 的患者对标准疗法表现出抵抗。靶向表皮生长因子受体 (EGFR) 已显着改善了许多癌症的临床结果。本研究免疫化学结果显示，116例PA样本中EGFR相关H-scores高于垂体，p21、p27-和Wif-1相关H-scores较低（P < 0.05 所有）。与低水平 EGFR 表达的患者相比，高水平 EGFR 的患者 PA 侵袭增加，总切除率更低，p21 和 p27 表达更低。双荧光素酶报告基因检测显示EGFR是miR-137的靶基因，miR-137模拟物可以抑制GH3细胞的增殖，诱导GH3细胞凋亡和G1期阻滞。与单独使用 miR-137 模拟物或 AZD9291 相比，miR-137 模拟物和 AZD9291 的组合对 GH3 细胞具有更强的抑制作用；此外，miR-137 抑制剂部分逆转了 AZD9291 的抑制作用。p21 和 p27 显示参与 miR-137 和 AZD9291 介导的对 GH3 细胞的影响。总之，PAs中EGFR的激活与肿瘤侵袭行为有关，这减少了患者PAs的总切除量。