Effect of TMP combined with cisplatin on expression of Mac2-BP and VEGF in Lewis lung cancer mice / 军事医学

ABSTRACT

Objective To investigate the effect of tetramethylpyrazine (TMP) combined with cisplatin(DDP) on the expression of Mac2-binding protein(Mac2-BP) and vascular endothelial growth factor (VEGF) in mice with lung cancer. Methods C57 BL/6 mice were subcutaneously inoculated with Lewis lung adenocarcinoma cells , and Lewis lung adenocarcinoma mouse xenograft model was established .Forty mice were randomly divided into four groupsnormal saline group(NS group,0.9%NaCl,0.2 ml), TMP group (TMP 100 mg/kg,0.2 ml), DDP group (DDP 2 mg/kg,0.2 ml), TMP plus DDP group (doses as above,0.2 ml totally) with 10 mice in each group.After 2 drug intervention,following 14 days of inoculation , the tumor diameter was measured every two days to calculate the tumor volume .The mice were sacrificed after 14 days of continuous medication , and the subcutaneous tumors were weighed after stripping to calculate the inhibitory rate.The expressions of Mac2-BP and VEGF was detected by Western blot and immunhistochemistry .Results Compared with NS group, the tumor growth rate of TMP group , DDP group and TMP+DDP group was slowed down , and the tumor growth rate in the TMP+DDP group was decreased most significantly .The inhibitory rate of TMP group , DDP group and TMP+DDP group was 25.57%, 45.24% and 66.5%,respectively.Kim, s formula was used to evaluate the synergy of the combined treatment .The q values for TMP +DDP group was 0.85 TMP and DDP in mice Lewis lung cancer .A positive correlation was observed between Mac 2-BP and VEGF expressions of NS group (Western blotting r=0.713,P=0.021,immunohistochemistry r=0.653, P=0.041). Compared with NS group, the expression of Mac2-BP and VEGF in the TMP group, DDP group, TMP+DDP group was dramatically decreased (P<0.05), and that in TMP +DDP group was significantly lower than in TMP and DDP groups (P<0.05 ).The results deduced by immunhistochemistry and Western blot were consistent.Conclusion Combination of TMP and cisplatin has additive anti-tumor effect on lung cancer bearing C 57BL/6 mice.It can inhibit tumor angiogenesis and the mechanism may be related to the inhibition of Mac 2-BP and VEGF expression .TMP can inhibit the growth of implanted Lewis lung carcinoma xenografted by inhibiting the expression of Mac2-BP and VEGF and the angiogenesis .TMP combined with DDP can improve the effect of chemotherapy and enhance the inhibiting effect of angiogenesis .Mac2-BP may promote the angiogenesis of lung cancer by up-regulating the expression of VEGF.