AG-1478

AG-1478是EGFR的抑制剂，在Ishikawa卵巢细胞系中作用于EGF诱导的Erk1/2磷酸化，IC50值为10 μM[1]。

EGFR（表皮生长因子受体）属于人HER-1家族，是一种细胞表面受体，由EGF家族（表皮生长因子家族）识别。多项研究表明，EGFR在多种实体瘤中过度表达，其过度表达预示着癌症患者预后差[1]。AG1478作为EGFR激酶抑制剂，阻断EGFR磷酸化以及超氧阴离子生成[2]。

与对照组相比，治疗人类肝细胞癌HA22T/VGH细胞可能会降低其抗肿瘤活性[3]。在卵巢癌细胞系CAOV-3或SKOV-3中，AG-1478可减弱EGFR信号[4]。用AG-1478处理人结直肠癌细胞株SW480后，EGFR磷酸化和细胞增殖均减少[5]。

在CAOV-3细胞异种移植nu/nu裸鼠模型中，AG-1478治疗可以减少EGFR磷酸化，从而限制肿瘤生长[4]。

Gong XD等人发现，AG-1478在NSCLC细胞系A549中通过FOXO3a可减少FOXM1的表达，A549细胞的化学敏感性增加[6]。

参考文献：
1.  Takai, N., et al., Synergistic anti-neoplastic effect of AG1478 in combination with cisplatin or paclitaxel on human endometrial and ovarian cancer cells. Mol Med Rep, 2010. 3(3): p. 479-84.
2.  D'Anneo, A., et al., Parthenolide induces superoxide anion production by stimulating EGF receptor in MDA-MB-231 breast cancer cells. Int J Oncol, 2013. 43(6): p. 1895-900.
3.  Bondi, M.L., et al., Entrapment of an EGFR inhibitor into nanostructured lipid carriers (NLC) improves its antitumor activity against human hepatocarcinoma cells. J Nanobiotechnology, 2014. 12(21): p. 1477-3155.
4.  Yu, Y., et al., Synergistic effects of combined platelet-activating factor receptor and epidermal growth factor receptor targeting in ovarian cancer cells. J Hematol Oncol, 2014. 7(1): p. 1756-8722.
5.  Yagublu, V., et al., Combination of the EGFR tyrosine kinase inhibitor AG1478 and 5-FU: no synergistic effect on EGFR phosphorylation, cell proliferation and apoptosis induction. Anticancer Res, 2013. 33(9): p. 3753-8.
6.  Gong, X.D., et al., [Effects of AG1478 on the expression of FOXM1 gene via FOXO3a in non-small cell lung cancer cells]. Zhonghua Zhong Liu Za Zhi, 2013. 35(8): p. 572-8.