目的 研究萘普替尼對(duì)表皮生長(zhǎng)因子受體（EGFR）不同突變亞型荷瘤小鼠腫瘤生長(zhǎng)的影響。方法 建立野生型EGFR人表皮鱗癌A431、L858R/T790M雙突變EGFR非小細(xì)胞肺癌H1975、Del19突變型EGFR非小細(xì)胞肺癌HCC827及HER2高表達(dá)的胃癌N87的裸鼠移植瘤模型，待腫瘤長(zhǎng)至100 mm³左右將小鼠分組，A431荷瘤小鼠分組：對(duì)照組、阿法替尼12 mg/kg和萘普替尼3.50、1.75、0.87、0.29 mg/kg；H1975荷瘤小鼠分組：對(duì)照組、阿法替尼30 mg/kg和萘普替尼7.00、3.50、1.75 mg/kg；HCC827荷瘤小鼠分組：對(duì)照組、阿法替尼12 mg/kg和萘普替尼3.50、1.75、0.87、0.60、0.29 mg/kg；N87荷瘤小鼠分組：對(duì)照組、阿法替尼12 mg/kg和萘普替尼7.00、3.50、1.75、0.87、0.29 mg/kg，每組10只動(dòng)物。分組后即開始ig給藥，對(duì)照組給予同體積去離子水，A431、H1975、HCC827、N87荷瘤小鼠分別給藥14、21、7、14 d。觀察相對(duì)腫瘤體積（RTV）、腫瘤增殖率及對(duì)腫瘤質(zhì)量的抑制率，在體考察萘普替尼的抗腫瘤作用。結(jié)果 A431荷瘤小鼠：與對(duì)照組比較，萘普替尼各劑量組RTV均顯著減小（P<0.01），腫瘤增殖率分別為26.6%、32.5%、34.8%、42.2%；瘤質(zhì)量均顯著降低（P<0.01），抑瘤率范圍在48.3%~73.9%；0.87 mg/kg為起效劑量，3.5 mg/kg劑量與阿法替尼12 mg/kg效果相當(dāng)，3.5mg/kg組小鼠體質(zhì)量顯著降低（P<0.01）。H1975荷瘤小鼠：與對(duì)照組比較，萘普替尼各劑量組RTV均顯著降低（P<0.05、0.01），腫瘤增殖率分別為14.5%、38.2%、65.3%；3.5 mg/kg為起效劑量，與阿法替尼30 mg/kg作用相當(dāng)；7.0、3.5 mg/kg組小鼠體質(zhì)量顯著降低（P<0.05、0.01）。HCC827荷瘤小鼠：與對(duì)照組比較，萘普替尼3.50、1.75、0.87、0.60 mg/kg組RTV降低極為顯著（P<0.01），腫瘤增殖率均小于40%；瘤質(zhì)量呈不同程度地降低，抑瘤率范圍52.9%~89.7%；0.6 mg/kg為起效劑量，1.75 mg/kg劑量與阿法替尼12 mg/kg作用相當(dāng)，3.5、1.75 mg/kg組小鼠體質(zhì)量顯著降低（P<0.01）。N87荷瘤小鼠：萘普替尼7.00、3.50、1.75 mg/kg組RTV及瘤質(zhì)量均顯著低于對(duì)照組（P<0.05、0.01），且腫瘤增殖率均小于40%，抑瘤率范圍54.9%~95.00%；1.75 mg/kg為起效劑量，3.5 mg/kg與阿法替尼12 mg/kg作用相當(dāng)；7.0、3.5 mg/kg組小鼠體質(zhì)量顯著降低（P<0.01）。結(jié)論 萘普替尼具有明顯的抗腫瘤作用，其中對(duì)EGFR野生型或單突變型荷瘤抗腫瘤作用較好。關(guān)鍵詞：萘普替尼；表皮生長(zhǎng)因子受體；表皮生長(zhǎng)因子受體酪氨酸激酶抑制劑；突變；非小細(xì)胞肺癌

Objective To study the effect of neptinib on the growth of tumors in mice bearing different EGFR mutant subtypes. Methods Xenograft models of wild-type EGFR human epidermal squamous cell carcinoma cell line A431, double mutant EGFR (L858R/T790M) non-small cell lung cancer cell line H1975, Del19 mutant EGFR non-small cell lung cancer cell line HCC827 and HER2 highly expressed gastric cancer cell line N87 in nude mice were established. The mice were divided into groups when the tumor grew to 100 mm³. A431 mice were divided into control group, alfatinib 12 mg/kg, naphtinib 3.50, 1.75, 0.87, 0.29 mg/kg; H1975 mice were divided into control group, alfatinib 30 mg/kg, naphtinib 7.00, 3.50, 1.75 mg/kg; HCC827 mice were divided into control group, alfatinib 12 mg/kg, naphtinib 3.50, 1.75, 0.87, 0.60, 0.29 mg/kg; N87 mice were divided into control group, alfatinib 12 mg/kg, naphtinib 7.00, 3.50, 1.75, 0.87, 0.29 mg/kg. Ten animals in each group. The mice in control group were given deionized water of the same volume. The mice bearing A431, H1975, HCC827 and N87 were ig given for 14, 21, 7 and 14 days respectively. To observe the relative tumor volume (RTV), the tumor growth rate and the tumor inhibition rate, which aims to investigate the antitumor effect of neptinib in vivo. Results A431 tumor-bearing mice:Compared with the control group, the RTV of each dose of Naprotinib decreased significantly (P<0.01), the proliferation rate of tumors was 26.6%, 32.5%, 34.8%, 42.2%, the tumour quality was significantly reduced (P<0.01), the inhibition rate ranged from 48.3% to 73.9%; 0.87 mg/kg was the effective dose, 3.5 mg/kg was equivalent to 12 mg/kg of Alphatinib, and the body weight of mice in 3.5 mg/kg group was significantly decreased (P<0.01). H1975 tumor-bearing mice:Compared with the control group, the RTV of each dose group of Naprotinib decreased significantly (P<0.05, 0.01), the proliferation rate of tumor was 14.5%, 38.2%, 65.3%, 3.5 mg/kg was the effective dose, which was equivalent to 30 mg/kg of Alfatinib, and the body weight of mice in 7.0 and 3.5 mg/kg groups decreased significantly (P<0.05, 0.01). HCC827 tumorbearing mice:Compared with the control group, the RTV of Naprotinib 3.50, 1.75, 0.87, 0.60 mg/kg group decreased significantly (P<0.01), and the proliferation rate of tumors was less than 40%. The tumour quality decreased in varying degrees, and the inhibition rate ranged from 52.9% to 89.7%. The effective dose was 0.6 mg/kg, and the dose of 1.75 mg/kg was equivalent to that of alfatinib 12 mg/kg, and the body weight of mice in 3.5 and 1.75 mg/kg groups decreased significantly (P<0.01). N87 tumor-bearing mice:RTV and tumor mass of naphtinib 7.00, 3.50, 1.75 mg/kg group were significantly lower than those of control group (P<0.05, 0.01), and the tumor proliferation rate was less than 40%, the inhibition rate ranged from 54.9% to 95.00%. 1.75 mg/kg was the effective dose, and the effect of 3.5 mg/kg was the same as that of afatinib 12 mg/kg; the body mass of mice in 7.0 and 3.5 mg/kg groups decreased significantly (P<0.01). Conclusion Neptinib has obvious anti-tumor effect, especially on tumors with wild-type or single-mutant EGFR.