Huang Yi, Yu Tao, Fu Xiaoyue, Chen Jiao, Liu Ying, Li Chunjie, Xia Yichao, Zhang Zhuoyuan, Li Longjiang
Department of Head and Neck Oncology, West China College of Stomatology, Sichuan University, and Department of Thoracic Cancer, West China Hospital, No,14, Section 3, Ren Min Nan Road, Chengdu, 610041, China.
BMC Cell Biol. 2013 Mar 9;14:13. doi: 10.1186/1471-2121-14-13.
Epidermal growth factor receptor (EGFR) is involved in the development of many human malignant tumors and plays an important role in tumor growth and metastasis. Antagonists of EGFR can suppress the growth of several malignancies; however, their therapeutic effect in adenoid cystic carcinoma (ACC) is controversial.
The increased proliferation of two ACC cell lines induced by EGF-treatment was reversed by nimotuzumab. Regardless of EGF stimulation, nimotuzumab-treated ACC cells were arrested in G1 phase and showed decreased expression of Ki67. In addition, EGF activated the MAPK-dependent pathway and up-regulated the expression of matrix metalloproteinase-9 and Snail, enhancing the invasive potential of an ACC cell line (ACC-M). The effects of EGF were down-regulated by nimotuzumab treatment.
These results suggest that nimotuzumab can inhibit the growth and invasion of ACC cells induced by EGF, probably through inactivation of ERK phosphorylation. Thus, nimotuzumab should be considered as a promising novel agent for the treatment of ACC.
表皮生长因子受体（EGFR）参与多种人类恶性肿瘤的发生发展，在肿瘤生长和转移中起重要作用。EGFR拮抗剂可抑制多种恶性肿瘤的生长；然而，其在腺样囊性癌（ACC）中的治疗效果存在争议。
尼妥珠单抗可逆转表皮生长因子（EGF）处理诱导的两种ACC细胞系增殖增加。无论有无EGF刺激，经尼妥珠单抗处理的ACC细胞停滞于G1期，且Ki67表达降低。此外，EGF激活丝裂原活化蛋白激酶（MAPK）依赖的信号通路，上调基质金属蛋白酶-9和Snail的表达，增强一种ACC细胞系（ACC-M）的侵袭能力。尼妥珠单抗处理可下调EGF的作用。
这些结果表明，尼妥珠单抗可能通过使细胞外信号调节激酶（ERK）磷酸化失活，抑制EGF诱导的ACC细胞生长和侵袭。因此，尼妥珠单抗应被视为一种有前景的治疗ACC的新型药物。
