Qiu Meng, Yi Cheng, Hou Mei
Division of Cancer Chemotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2006 Jul;37(4):534-7.
To investigate the antiangiogenic and antitumor effects of combined low-dose cyclophosphamide(CTX) and paclitaxel(PTX).
In this experiment, Lewis lung carcinoma model was established in C57BIL6 mice. Forty mice were randomly divided into four groups: control group, cyclophosphamide (170 mg/kg, q6d) group, paclitaxel (10 mg/kg, q7d) group, and cyclophosphamide plus paclitaxel group. The growth of tumor and the sideeffect of each therapy were investigated. Microvessel density (MVD) was assessed by CD31 immunostaining, and immunohistochemistry (IHC) image analysis was performed for semiquantification of vascular enthothelial growth factor (VEGF).
The combined low-dose therapy with cyclophosphamide and paclitaxel was most effective for antagonizing tumor-associated angiogensis; the mice of this group had the lowest MVD and VEGF expression, compared to mice of other groups (P < 0.005). The combination therapy also brought about higher antitumor rate, lower tumor volume, and lower tumor weight than did the single therapy (P < 0.005). Paclitaxel (10 mg/kg, q7d) therapy had the slightest side-effects; other therapies had similar acceptable side effects.
The combined use of low dose cyclophosphamide and paclitaxel has synergistic antiangiogenic effect on the mouse model of Lewis lung carcinoma; the combination of these two agents is clearly more effective for inhibiting angiogenesis and growth of tumor.
探讨低剂量环磷酰胺（CTX）与紫杉醇（PTX）联合应用的抗血管生成及抗肿瘤作用。
本实验采用C57BIL6小鼠建立Lewis肺癌模型。40只小鼠随机分为四组：对照组、环磷酰胺（170mg/kg，每6天一次）组、紫杉醇（10mg/kg，每7天一次）组以及环磷酰胺加紫杉醇组。观察肿瘤生长情况及各治疗方法的副作用。通过CD31免疫染色评估微血管密度（MVD），并采用免疫组织化学（IHC）图像分析对血管内皮生长因子（VEGF）进行半定量分析。
低剂量环磷酰胺与紫杉醇联合治疗对拮抗肿瘤相关血管生成最为有效；与其他组小鼠相比，该组小鼠的MVD和VEGF表达最低（P<0.005）。联合治疗的抗肿瘤率也高于单一治疗，肿瘤体积和肿瘤重量更低（P<0.005）。紫杉醇（10mg/kg，每7天一次）治疗的副作用最小；其他治疗的副作用程度相近，均可接受。
低剂量环磷酰胺与紫杉醇联合应用对Lewis肺癌小鼠模型具有协同抗血管生成作用；二者联合在抑制血管生成和肿瘤生长方面明显更有效。
