| 名稱 | Gefitinib |
| 描述 | Gefitinib (ZD1839) is an EGFR first-generation inhibitor with oral activity that inhibits the EGFR 19 Del and L858R mutations. Gefitinib has antitumor activity and is used for the treatment of EGFR-mutated non-small-cell lung cancers. Gefitinib administration RESULTS in the development of the EGFR C797S resistance mutation. |
| 細(xì)胞實(shí)驗(yàn) | The human NSCLC H1299, H1975, A549, H460, GLC82, H460, and CALU-3 cell lines were provided by the American Type Culture Collection and maintained in RPMI-1640 supplemented with 10% FBS in a humidified atmosphere with 5% CO2. CALU-3 GEF-R is a cell line obtained in vitro as previously described. Briefly, over a period of 12 months, human CALU-3 lung adenocarcinoma cells were continuously exposed to increasing concentrations of gefitinib. The starting dose was the dose causing the inhibition of 50% of cancer cell growth (IC50; gefitinib, 1 μmol/L). The drug dose was progressively increased to 15 μmol/L in approximately 2 months, to 20 μmol/L after other 2 months, to 25 μmol/L after additional 2 months, and, finally, to 30 μmol/L for a total of 12 months. The established resistant cancer cell lines were then maintained in continuous culture with the maximally achieved dose of each TKI that allowed cellular proliferation (30 μmol/L for each drug) [2]. |
| 動物實(shí)驗(yàn) | Four- to 6-week old female balb/c athymic (nu+/nu+) mice were purchased from Charles River Laboratories. Mice were acclimatized for 1 week before being injected with cancer cells and injected subcutaneously with 107 H1299 and CALU-3 GEF-R cells that had been resuspended in 200 μL of Matrigel. When established tumors of approximately 75 mm3 in diameter were detected, mice were left untreated or treated with oral administrations of metformin (200 mg/mL metformin diluted in drinking water and present throughout the experiment), gefitinib (150 mg/kg daily orally by gavage), or both for the indicated time periods. Each treatment group consisted of 10 mice. Tumor volume was measured using the formula π/6 × larger diameter × (smaller diameter)2. Tumor tissues were collected from the xenografts and analyzed by Western blotting for the expression and activation of EGFR, AMPK, mitogen-activated protein kinase (MAPK), and S6 [2]. |
| 體外活性 | 方法：23 種腫瘤細(xì)胞用 Gefitinib 處理 72 h，使用 MTT 方法檢測細(xì)胞活力。
結(jié)果：只有 PC9 細(xì)胞系的 IC50<1 μmol/L (高度敏感)，14 個細(xì)胞系的 IC50>10 μmol/L (抗性)，其余 8 個細(xì)胞系具有 1-10 μmol/L 的 IC50 (中等敏感）。[1]
方法：腫瘤細(xì)胞 HT29、KB、Du145 和 A549 用 Gefitinib (0.032-50 μM) 處理 2 h，在細(xì)胞裂解前五分鐘加入 EGF (0.1 μg/mL)，使用 Western Blot 方法檢測靶點(diǎn)蛋白表達(dá)水平。
結(jié)果：Gefitinib 在所有腫瘤細(xì)胞系中產(chǎn)生 EGFR 自磷酸化的劑量依賴性抑制。[2] |
| 體內(nèi)活性 | 方法：為檢測體內(nèi)抗腫瘤活性，將 Gefitinib (3.125-200 mg/kg in 0.5% polysorbate 80) 口服給藥給攜帶腫瘤 A431、 Du145 或 A549 的 nude 小鼠，每天一次，持續(xù)七-十五天。
結(jié)果：Gefitinib 劑量依賴性方式抑制 A431、 Du145 或 A549 腫瘤生長。[2]
方法：為檢測體內(nèi)抗腫瘤活性，將 Gefitinib (40 mg/kg，每天一次) 或 Gefitinib (200 mg/kg，每五天一次) 灌胃給藥給攜帶人肺癌腫瘤 H3255 的 athymic nude 小鼠，持續(xù)兩周。
結(jié)果：每周治療顯示出比每天治療更好的抑制作用。與每日給藥方案相比，每周給藥方案對 p-EGFR、p-ERK 和 p-AKT 的抑制作用更強(qiáng)。[3] |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 18.33 mg/mL (41.02 mM)
Ethanol : 4.5 mg/mL (10 mM)
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 4.47 mg/mL (10 mM), Please add co-solvents sequentially, clarifying the solution as much as possible before adding the next one. Dissolve by heating and/or sonication if necessary. Working solution is recommended to be prepared and used immediately.
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| 關(guān)鍵字 | EGFR tyrosine kinase | Autophagy | lung cancer | breast cancer | phosphorylation | Inhibitor | Apoptosis | inhibit | TAMs | NSCLCs | EGFR | antitumour | Epidermal growth factor receptor | HER1 | tumor metastasis | Gefitinib | ZD-1839 | ZD 1839 | ErbB-1 |
| 相關(guān)產(chǎn)品 | Oxyresveratrol | Guanidine hydrochloride | Naringin | Valproic Acid | Taurine | Aceglutamide | Hydroxychloroquine | Curcumin | Stavudine | Salicylic acid | Paeonol | Sodium 4-phenylbutyrate |
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