Objective To explore the effects and mechanism of low-dose metronomic (LDM) chemotherapy on VEGF-C/Flt-4 axis in lung adenocarcinoma A54 9 cell xenografts in nude mice. Methods The human lung adenocarcinoma A54 9 cells were seeded in 18 nude mice to establish tumor-bearing animal models. They were divided into maximum tolerated dose (MTD) group (CTX 100 mg ? Kg-1 intraperitoneal injection every other day,3 consecutive times;n =6), LDM group (CTX 20 mg ? Kg-1 ? D-1 intraperito-neal injection,n= 6) and control group (0. 1 mL. Saline intraperitoneal injection once daily,n = 6) according to a random number table. The nude mice were sacrificed by neck luxation after 21 days of treatment, and subcutaneous tumor tissue were subjected to streptavidin-perosidase(SP) immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) for VEGF-C, Flt-4 protein and mRNA expression detection, respectively. Results VEGF-C,Elt-4 protein and mRNA expression level in tumor tissue of nude mice in LDM group were significantly lower than those in MTD group and control group (P<0. 05). Conclusion LDM chemotherapy may reduce lymphatic metastasis of lung adenocarcinoma A54 9 cell xenografts in nude mice through decreasing VEGF-C,Flt-4 expression in tumor tissue.%目的 探讨持续小剂量(LDM)化疗对肺腺癌A549细胞荷瘤裸鼠肿瘤组织中血管内皮生长因子-C(VEGF-C)/fms-样酪氨酸激酶-4(Flt-4)轴的影响及其机制.方法 将人肺腺癌A549细胞接种于18只裸鼠皮下,建立荷瘤动物模型,以随机数字表法将其分为最大耐受剂量(MTD)组(CTX 100 mg·kg-1腹腔注射,隔日1次,连续3次;n=6)、LDM组(CTX 20 mg·kg-1·d-1腹腔注射,n=6)和对照组(0.1 mL生理盐水腹腔注射,1次/d;n=6).治疗21 d后脱颈处死裸鼠,取皮下肿瘤组织,采用免疫组织化学链霉素抗生物素蛋白-过氧化物酶(SP)法及逆转录聚合酶链反应(RT-PCR)分别检测肿瘤组织中VEGF-C、Flt-4的蛋白及mRNA表达.结果 LDM组裸鼠肿瘤组织VEGF-C、Flt-4蛋白及mRNA的表达水平均显著低于MTD组和对照组(P<0.05).结论 LDM化疗可能通过降低肿瘤组织VEGF-C、Flt-4的表达而减少肺腺癌A549荷瘤裸鼠肿瘤的淋巴转移.
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