Icotinib is an epidermal growth factor receptor (EGFR; IC₅₀=5nM) inhibitor that targets mutants such as EGFR (L858R, T790M, L861Q)[1-2]. Icotinib blocks tumor cell proliferation signals by inhibiting EGFR tyrosine kinase autophosphorylation and promotes tumor cell death through activation of apoptotic pathways, primarily utilized in non-small cell lung cancer research[3-4].
In vitro, Icotinib (2μM) was administered to PC-9/GR and H1975 non-small cell lung cancer cells for 4 weeks. Icotinib upregulated ATG7 expression via the STAT3/FOXM1 signaling pathway, inducing protective autophagy, thereby inhibiting Icotinib-induced apoptosis and enhancing drug resistance[5]. Treatment of A549 non-small cell lung cancer cells with Icotinib (0.01–10μM) for 24-72 hours, Icotinib exerted concentration-dependent inhibitory effects on cell proliferation, migration, and invasion. Icotinib suppressed the the epithelial-mesenchymal transition (EMT) process[6].
In vivo, Icotinib (50mg/kg) was orally administered to BALB/c nude mice bearing H1975 xenograft tumors (starting at a tumor volume of approximately 100mm³, three times per week for 5 weeks). Icotinib monotherapy only slightly reduced tumor volume, whereas its combination with Chidamide (12.5mg/kg or 25mg/kg) significantly suppressed tumor growth[7]. Icotinib (100mg/kg) was orally administered to BALB/c nude mice bearing PC9 xenograft tumors (starting on day 10 post-implantation, once daily for 18 days). Icotinib alone inhibited tumor growth, and a more pronounced antitumor effect was observed when combined with Thalidomide (200mg/kg)[8].
References:
[1] Tan F, Shen X, Wang D, et al. Icotinib (BPI-2009H), a novel EGFR tyrosine kinase inhibitor, displays potent efficacy in preclinical studies. Lung Cancer. 2012 May;76(2):177-82.
[2] Zhao Q, Cheng J, Chen P, et al. Icotinib: efficacy in different solid tumors and gene mutations. Anticancer Drugs. 2020 Mar;31(3):205-210.
[3] Guan YS, He Q, Li M. Icotinib: activity and clinical application in Chinese patients with lung cancer. Expert Opin Pharmacother. 2014 Apr;15(5):717-28.
[4] Li N, Ou W, Cheng C, et al. Adjuvant icotinib for resected EGFR-mutated stage II-IIIA non-small-cell lung cancer (ICTAN, GASTO1002): a randomized comparison study. Signal Transduct Target Ther. 2025 Aug 28;10(1):273.
[5] Lyu X, Zeng L, Shi J, et al. Essential role for STAT3/FOXM1/ATG7 signaling-dependent autophagy in resistance to Icotinib. J Exp Clin Cancer Res. 2022 Jun 11;41(1):200.
[6] Wang GH, Hu ZY. Icotinib inhibits proliferation and epithelial-mesenchymal transition of non-small cell lung cancer A549 cells. Math Biosci Eng. 2019 Aug 21;16(6):7707-7718.
[7] Zhang N, Liang C, Song W, et al. Antitumor activity of histone deacetylase inhibitor chidamide alone or in combination with epidermal growth factor receptor tyrosine kinase inhibitor icotinib in NSCLC. J Cancer. 2019 Jan 29;10(5):1275-1287.
[8] Sun X, Xu Y, Wang Y, et al. Synergistic Inhibition of Thalidomide and Icotinib on Human Non-Small Cell Lung Carcinomas Through ERK and AKT Signaling. Med Sci Monit. 2018 May 15;24:3193-3203.
Icotinib表皮生长因子受体（EGFR；IC50=5nM）抑制剂，可抑制EGFR（L858R，T790M，L861Q）等突变体[1-2]。Icotinib可抑制EGFR酪氨酸激酶的自磷酸化来阻断肿瘤细胞增殖信号，同时通过激活凋亡通路以促进肿瘤细胞死亡，主要被用于非小细胞癌的相关研究[3-4]。
在体外，Icotinib（2μM）处理PC-9/GR和H1975非小细胞肺癌细胞4周，Icotinib通过STAT3/FOXM1信号通路上调ATG7表达，诱导保护性自噬，从而抑制Icotinib引发的细胞凋亡并增强耐药性[5]。Icotinib（0.01–10μM）处理A549非小细胞肺癌细胞24-72小时，Icotinib以浓度依赖性方式抑制细胞增殖与迁移侵袭能力，同时阻断上皮-间质转化（EMT）进程[6]。
在体内，Icotinib（50mg/kg）口服给药处理荷瘤（H1975细胞）BALB/c裸鼠（从肿瘤体积约100mm³开始，每周三次，持续5周），Icotinib单药治疗仅导致肿瘤体积轻微减小，而与Chidamide（12.5mg/kg或25mg/kg）联合使用时，则显著抑制肿瘤生长[7]。Icotinib（100mg/kg）口服给药处理荷瘤（PC9细胞）BALB/c裸鼠（从接种细胞后第10天开始，每日一次，持续18天），Icotinib单药治疗可抑制肿瘤生长，与Thalidomide（200mg/kg）联合使用时有更好的抑制肿瘤效果[8]。