[Combined low-dose chemotherapy inhibiting angiogenesis and growth of Lewis lung cancinoma xenografts in mice].
OBJECTIVE
To investigate the antiangiogenic and antitumor effects of combined low-dose cyclophosphamide(CTX) and paclitaxel(PTX).


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Qiu
Meng
M
Division of Cancer Chemotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
Yi
Cheng
C
Hou
Mei
M
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D017239:Paclitaxel / Q000008:administration & dosage; D011897:Random Allocation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D003520:Cyclophosphamide; D017239:Paclitaxel