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OBJECTIVE To further explore the function of combine use of tetramethylpyrazine (TMP) and cisplatin (DDP) in lung carcinoma. METHODS We used the combination drug to treat Lewis lung cancer mice, investigated the expression level of vascular endothelial growth factor (VEGF), Kruppel-like factor 4 (KLF4) and A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) and to further explore the inhibitory effects and potential mechanism of TMP combined with DDP on tumor angiogenesis. RESULTS The tumor growth was suppressed in TMP group, DDP group and TMP combined with DDP group. Furthermore, the weights and volume of tumor, the expression level of VEGF, KLF4 and ADAMTS1 were found significantly changed between experiment group and control group. These findings suggest that TMP with DDP had additional or synergistic effects to inhibit the tumor growth effectively, might be achieved through reducing the expression of angiogenesis promoting factor VEGF and increasing expression of angiogenesis inhibitors KLF4 and ADAMTS1. CONCLUSION KLF4 and ADAMTS1 may be synergically involved in the angiogenesis in mouse Lewis lung cancer through the different signal ways.