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目的探讨重组人血管内皮抑素注射液恩度(endostar)对非小细胞肺癌淋巴转移的抑制作用。方法于裸鼠右侧腋窝经皮下注射A549肺癌细胞(1×107/mL,0.2mL)建立裸鼠荷瘤模型,选择建模成功的56只裸鼠随机分为8组(n=7):对照组(生理盐水0.2mL,1次/d),顺铂组(顺铂20μg,隔日1次),3种浓度恩度组(恩度2、4、6mg/kg,1次/d),3种浓度恩度+顺铂(恩度2、4、6mg/kg,1次/d;顺铂20μg,隔日1次)。所有实验用药均经尾静脉注射,连续给药14d。给药结束后观察7d,测量并记录肿瘤直径,统计各组肿瘤大小的变化。处死裸鼠,对肿瘤组织及可疑转移淋巴结采用H-E染色和免疫组织化学染色,并计算各组淋巴转移阳性率、转移淋巴结数目及微淋巴管密度。结果各用药组给药后与给药前肿瘤直径差值均小于对照组(P<0.05),且3种浓度恩度+顺铂组的肿瘤直径差值均小于3种浓度恩度组和顺铂组(P<0.05)。3种浓度恩度组和3种浓度恩度+顺铂组的淋巴转移阳性率、转移淋巴结数目及微淋巴管密度均低于对照组和顺铂组(P<0.05);6mg/kg恩度组和6mg/kg恩度+顺铂组淋巴转移阳性率、转移淋巴结数目及微淋巴管密度均低于2、4mg/kg恩度组和2、4mg/kg恩度+顺铂组(P<0.05)。结论恩度和顺铂均能抑制非小细胞肺癌肿瘤生长,恩度与顺铂联合使用对肿瘤生长的抑制作用强于两者单独使用;恩度能够抑制肿瘤微淋巴管生成及肿瘤淋巴转移,且作用强度与浓度有关,顺铂未发现类似作用。
Objective To investigate the inhibitory effect of recombinant human endostar injection on lymphatic metastasis in non-small cell lung cancer. Methods The nude mice bearing tumor model was established by subcutaneous injection of A549 lung cancer cells (1 × 107 / mL, 0.2 mL) in the armpit on the right side of nude mice. 56 nude mice with successful modeling were randomly divided into 8 groups (n = 7) The rats in the control group (saline 0.2 mL, once daily), cisplatin group (cisplatin 20 μg, every other day), three concentrations of Endostar (Endurance 2,4,6 mg / kg, once daily) Three concentrations of Endostar + Cisplatin (Endurance 2,4,6 mg / kg, 1 / d; cisplatin 20μg, every other day). All experimental drugs were injected through the tail vein, continuous administration 14d. After the administration for 7 days, the diameter of tumor was measured and recorded, and the change of tumor size was calculated. The nude mice were sacrificed and the tumor tissues and suspicious metastatic lymph nodes were stained with H-E and immunohistochemistry. The positive rate of lymph node metastasis, the number of metastatic lymph nodes and the lymphatic vessel density were calculated. Results The difference of tumor diameter between before treatment and after administration was less than that of the control group (P <0.05), and the difference of tumor diameter between the three concentrations of Endostar + cisplatin group was less than three kinds of concentrations Platinum group (P <0.05). The positive rate of lymph node metastasis, the number of metastatic lymph nodes and the lymphatic vessel density in the three concentrations of Endostar group and the three concentrations of Endostar + cisplatin group were lower than those in the control group and cisplatin group (P <0.05) The positive rate of lymph node metastasis, the number of metastatic lymph nodes and the lymphatic vessel density in the group of 6mg / kg Ende and cisplatin were lower than those in the group of 2,4 mg / kg ende and 2,4 mg / kg ende + cisplatin (P < 0.05). Conclusions Endothelium and cisplatin can both inhibit the growth of non-small cell lung cancer. The combination of Endostar and cisplatin is more effective than cisplatin in the inhibition of tumor lymphangiogenesis and tumor lymphatic metastasis. And the intensity and concentration, cisplatin did not find a similar effect.