Effect Of Tetramethyl Pyrazine Combined With Cisplatin On Growth And Expression Of VEGF,Gal-1 And Tumstatin Of Lewis Lung Cancer Rats

As environmental pollution and unhealthy living habits, the increasing cancer incidence, mortality year by year, while lung cancer in the malignant tumor mortality in first place. At present the treatment of lung cancer are mainly composed of surgery, radiotherapy, chemotherapy, much complications and poor prognosis, which puts forward new problems for clinical treatment. Malignant tumor growth and metastasis depend on angiogenesis, inhibiting angiogenesis can inhibit tumor growth and metastasis. Tumor angiogenesis is dependent on angiogenesis promotes balance adjustment between the factors and inhibiting factor. Vascular endothelial growth factor(VEGF) is widely recognized as the strongest effect on promoting angiogenesis factor; Galectin-1(Gal-1) is one of the most important members of the family of Galectins, promoting tumor angiogenesis affects tumor cell growth; Tumstatin is found that the activity of the most powerful endogenous tumor angiogenesis inhibiting factor, can directly promote the apoptosis of tumor cells. Tetramethylpyrazine(TMP) is the main components of traditional Chinese medicine Chuanxiong, is an inhibitor of new blood vessel growth. Cisplatin(DDP) is one commonly used in clinical treatment of lung cancer, is the most effective single agent.In recent years, studies have shown that combination of vascular growth inhibitor and chemotherapy drugs can improve the effect of the treatment of tumor. In this experiment, by observing the effects of TMP and DDP on growth of transplantation tumor in mice Lewis lung cancer, immunohistochemistry(IHC) and Western blot method for detection of the expression of VEGF, Gal-1 and Tumstatin, on the basis of all this,the paper analyzes their mutual relationship.In this experiment the Lewis lung carcinoma cells were injected into healthy C57BL/6 mice subcutaneously in the right axilla 0.2 ml, copy a transplanted tumor model of Lewis lung cancer. Then randomly divided into 4 groups: control group, DDP group, TMP group, and combination group, each 10 rats. Different treatments were served for 14 days, then all of rats were put to death. In the past 14 days, the subcutaneous tumors were weighted, then to calculate inhibitory rate and observe tumor cells and vascular structure under electron microscope.The expression of VEGF and Gal-1 were detected by IHC and Western-blotIt was found that the control group tumors grow fastest, slowest combination group, DDP group lower than the TMP group. The growth inhibition rate in combination group(59.81%) was significantly higher than that in TMP group(20.42%) and DDP group(34.65%). That TMP, DDP can effectively inhibit the growth of Lewis lung cancer transplanted tumor,the combination of the two drugs inhibited the enhancement. We observed the tumor cell structures under the electron microscope, the control group:larger nucleolus, abundant organelles, dense tumor cell distribution. The difference was not significant in the other three groups: broken pieces of the nucleolus, scarce organelles, mitochondria swelling. But the vascular structures had no obvious change. IHC shows : The VEGF and Gal-1expression of combination group were significantly lower than the other group(p<0.01). The Tumstatin expression of combination group was obviously strengthener than the other group 3(p<0.01). Western blot also illustrates this result. Experiment shows that TMP and DDP could inhibit the expression of VEGF and Gal-1, promote the expression of Tumstatin,combined with inhibition / promote. Pearson correlation analysis shows:the expression of VEGF had positive correlation with Gal-1(r=0.638, P=0.047). Negative correlation with Tumstatin(r =-0.707, P<0.05). Tip Gal-1, Tumstatin may be associated with tumor angiogenesisrelated.In summary that both TMP and DDP can effectively inhibit the growth of Lewis lung cancer transplanted tumor, the combination of the two drugs inhibited the enhancement. Effect of the combination of the two drugs could inhibit the expression of VEGF and Gal-1, promote the expression of Tumstatin to inhibit tumor angiogenesis and inhibit tumor growth. The effect was stronger after combined.