| Objective To study the mechanism of TNP-470 effecting on the growth , metastasis of lung Adenocarcinoma LA795 in mice, the experiment is designed to observe the inhibitory effect of angiogenesis inhibitor TNP-470 alone or combination with CTX.Methods Forty T739 mice bearing high metastatic LA795 tumor cells were randomized into five groups: Group A (control group) ; Group B (vehicle group) ; Group C (TNP-470 30 mg/kg); Group D (CTX 40 mg/kg); Group E (TNP-470 30 mg/kg+CTX 40 mg/kg). Different treatments were served from day 4 after lung Adenocarcinoma LA795 transplantation and all mice were sacrificed after 24 days, the lenghth and width of tumor subcutaneously transplanted were measured by vernier calipers at every four days during the therapy time. The volume was calculated.The weight of primary tumors subcutaneously transplanted and the node of spontaneous lung metastasis were examined at 24th day after all mice sacrificed .The inhibitory rate of weight of tumor subcutaneous transplanted and spontaneous lung metastasized node were calculated .The primary tumor subcutaneous transplanted and lungs of all mice were processed for histological examination. The expression of P-selectin ,bFGF, MVD (microvessel density), PCNA (Proliferation cell nuclear antigen), in subscutaneous tumor issue, were detected by immunohistochemical method;The apoptosis in tumors subscutaneous transplanted was detected by biotinyated - dUTP nick and labeling (TUNEL) method.Results 1. In every treatment group tumor growth was suppressed significantly, Group E showed significant enhancement efficacy in anti-tumor growth. 2 . TNP-470 can decreased the weight of tumorsubcutaneous transplanted , combination with CTX could produce synergetic efficacy . the weight of tumor were 3. 92±0. 54g, 3. 81+0. 43g, 2. 69±0. 18g, 2. 13±0.29g, 0.72 + 0. 07g . 3^ TNP-470 can decreased the node number of spontaneaously metastasis , Group E showed obviously enhancement efficacy in anti-tumor metastasis .The number of spontaneously lung metastasis nodes were respectively 12. 13 ±4. 02, 11. 75 ±3. 59, 4. 75 ±3. 34, 8.50 + 2.67,1.75 + 1. 71^ TNP-470 could induce apoptosis of tumor cells, but had no effects prohibiting the expression of PCNA in tumor cells , thus having no obviously effect on s-phase fraction(SPF). The apoptosis rates of A Group C> Group Dn Group E Group tumor cells (AR) subcutaneous transplanted was 16.1 + 3. 25, 25. 42 ±4.80, 28. 3 + 3. 67,38. 25 + 3. 67, respectively. 5^ Contrary to CTX, The expression of subscutaneous tumor MVD, P-selectin and bFGF were inhibited by TNP-470 compared with A group(R0. 0U R0. 01), especioully obviouslly inhibited in E group, the average value of P-selectin was 13. 75+3. 38,13. 37+4. 2 , 7.13±3. 01,11. 50±3. 64, 5. 25 +2. 27,respectively. 6> Through linear correlation test, the expression of P-selectin in tumor had positive correlation with the number of lung metastatic nodes (r=0.86, K0. 01)Conclusion1. Angiogenesis inhibitor TNP-470 could down-regulation of bfgf (basic fibroblast growth factor) expresssion and could suppress formation of new blood vessels in tumors subscutaneous transplanted. 2. Angiogenesis inhibitor TNP-470 could inhibit tumor growth , lung metastasis of lung adenocarcinoma LA795, Combination with CTX could produce synergetic effect .3. Angiogenesis inhibitor TNP-470 could induce apoptosis of tumor cells of lung adenocarcinoma LA795.4. Angiogenesis inhibitor TNP-470 could inhibit the expression of P-selectin in tumors subscutaneous transplanted. The fact that TNP-470 inhibited tumor metastasis may be associated its effect of suppressing...
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