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背景与目的:血管生成抑制剂联合化疗药物治疗肿瘤成为目前研究热点之一。本研究旨在观察烟曲霉醇(fumagillol,TNP-470)联合环磷酰胺(cyclophosphamide,CTX)对肺腺癌小鼠异体移植转移的协同抑制作用,并初步探讨TNP-470抑制肿瘤转移的相关机制。方法:将40只接种高转移性LA795肺腺癌细胞的T739裸小鼠随机分成5组:对照组、溶剂组、TNP-470组(30mg/kg)、CTX组(40mg/kg)、联合组(TNP-47030mg/kg+CTX40mg/kg)。实验3周后,处死全部小鼠。剥离皮下肿瘤称瘤重并计算抑瘤率;取出双肺观察表面肿瘤转移情况,计算肿瘤肺转移发生率,计数各组小鼠肺表面转移结节数及计算出肺表面结节转移抑制率。免疫组化和图像分析系统检测皮下移植瘤中微血管密度(microvesseldensity,MVD)、P-选择素表达并定量分析。结果:联合组抑瘤率(81.5%)明显高于其他各组(P<0.01),Q值等于1.21,说明两药合用具有协同作用。与对照组(12.13±4.02)相比,联合组(1.75±1.71)、TNP-470组(4.75±3.34)、CTX组(8.50±2.67)肺表面转移结节数明显下降;同时TNP-470组和联合用药组皮下肿瘤内MVD、P-选择素表达与对照组相比均下降,差异有显著性(P<0.01),而CTX组对此则无明显影响。结论:TNP-470与CTX对LA795肺腺癌的肺结节转移具有协同抑制作用;TNP-470抑制LA795肺腺癌转移与其抑制肿瘤内P-选择素表达有关。
BACKGROUND & OBJECTIVE: Angiogenesis inhibitors combined with chemotherapeutic drugs have become one of the hot topics in the field of cancer research. This study aimed to observe the synergistic inhibitory effect of fumagillol (TNP-470) combined with cyclophosphamide (CTX) on allograft metastasis of lung adenocarcinoma mice and to investigate the related mechanism of TNP-470 inhibiting tumor metastasis . Methods: T739 nude mice inoculated with highly metastatic LA795 lung adenocarcinoma cells were randomly divided into five groups: control group, solvent group, TNP-470 group (30mg / kg), CTX group (TNP-47030 mg / kg + CTX 40 mg / kg). Three weeks after the experiment, all mice were sacrificed. Peel the subcutaneous tumor and calculate the tumor inhibition rate; remove the lungs to observe the surface tumor metastasis, calculate the incidence of lung metastasis, count the number of pulmonary metastases in each group of mice and calculate the pulmonary nodule metastasis rate. Immunohistochemistry and image analysis system were used to detect microvessel density (MVD) and P-selectin expression and quantitative analysis in subcutaneous xenografts. Results: The inhibition rate (81.5%) in the combination group was significantly higher than that in other groups (P <0.01), and the Q value was equal to 1.21, indicating that the combination of the two drugs had a synergistic effect. Compared with the control group (12.13 ± 4.02), the numbers of pulmonary metastasis nodules in the combined group (1.75 ± 1.71), TNP-470 group (4.75 ± 3.34) and CTX group (8.50 ± 2.67) Compared with the control group, the expression of MVD and P-selectin in the subcutaneous tumor of the combination group and the control group decreased significantly (P <0.01), while the CTX group had no significant effect. Conclusions: TNP-470 and CTX have a synergistic inhibitory effect on lung nodule metastasis of LA795 lung adenocarcinoma. TNP-470 inhibits the metastasis of LA795 lung adenocarcinoma and inhibits the expression of P-selectin in the tumor.