To Study Inhibition Effect And Mechanism By Danshen United CTX With Lewis Lung Cancer Rats

Hypoxia is paid more and more attention on in recent years. With the rapid growth of solid tumors, tumor tissue appears low oxygen concentrations within the area. Hypoxia-inducible factor HIF-la mRNA plays an important role on the tumor hypoxia signal molecules transduction. Hypoxia increases the invasiveness of the tumor, and resistances the role of chemotherapy. How to change the state of tumor hypoxia, is another anti-tumor research problems. Salvia has the role of blood circulation, improves microcirculation, reduces blood viscosity and dilation of blood vessels, and scavenges oxygen free radicals. In theory, the Salvia has a role in improving the state of tissue hypoxia.This study aims to observe cyclophosphamide (CTX) and Danshen injection drug combinations, To detection of tumor cells of hypoxia-inducible factor-la(HIF-lamRNA) expression and the concentration of vascular endothelial growth factor (VEGF) in serum, Observe whether Danshen injection synergistic inhibition of Lewis lung tumor angiogenesis, reduce the number of hypoxia cells to tumor, Thereby enhancing the cyclophosphamide (CTX) on the inhibition rate of solid tumors and induce apoptosis, and enhance chemotherapy.Methods(1)Model:The tumor cell suspension which was made from the rats Lewis lung tumor tissue passed on behalf of the 14-day,was inoculated in subcutaneously of right lower limb of 60 healthy female C57BL/6 mice that weighed 16-18g.(2)Groups:Randomly divided into six groups, each team 10, namely, Normal control Group (Physiological saline),Danshen Group(Salvia injection 20 mg/kg), CTX Group (cyclophosphamide 20mg/kg), Combined Group 1 (Salvia injection 10ml/kg + cyclophosphamide 20mg/kg),Combined Groups 2 (Salvia injection 20ml/kg + cyclophosphamide 20mg/kg),Combined Groups 3 (Salvia injection 40ml/kg + cyclophosphamide 20mg/kg)(3)Dose and time:Each group was inoculated for 10 days by intraperitoneal injection 0.2ml/one rat, after the second day.(4)Sampling and testing indicators:By obtaining orbital blood, The routine blood testing and vascular endothelial growth factor expression levels were determined after 24 hours of the last administer; the quality of the tumors were measured to calculate the inhibition rate;the expression of HIF-la mRNA in tumor cells were determined, the microvessel density of tumor,the characteristics of apoptotic cells and the number of organ metastasis were observed on electron microscope.Results1.Salvia injection combined with CTX on Lewis lung cancer have better therapeutic effect, the inhibition rates were 68.00%,77.04%,55.83%. Compared with the CTX group, the Joint Group 2 tumor weight significantly reduced, the difference was statistically significant (P<0.01).2.Compared with the control group, HIF-la mRNA levels of Danshen group,CTX group,Combined Group 1,Combined Group 2,Combined Group3, decreased significantly (P<0.01). Compared with the CTX group, HIF-la mRNA expression values of Combined Group 1,Combined Group 2,Combined Group3, trended to decrease, but the difference was not statistically significant (P>0.05).3.Compared with the control group, CTX group, Combined Group 1,Combined Group 2,Combined Group3 of the of the serum VEGF expression levels decreased significantly (P<0.01). Compared with the CTX group, Combined Group 1,Combined Group 2,Combined Group 3 of the of the serum VEGF expression levels decreased, but the difference was not statistically significant (P>0.05).4. Compared with the CTX group, tumor microvessel density of Combined Group 2 was significantly lower, the difference was statistically significant (P<0.01).5. Compared with the CTX group, apoptotic index of Combined Group 2 increased, the difference was statistically significant (P<0.05). 6.Compared with the CTX group, white blood cell count of Combined Group 1 Combined Group 2, was significantly lower, the difference was statistically significant (P<0.05).7.The total transfers number of the control group,Danshen group,CTX group, were 1,2,0. The combined group 1, combined group 2, combined group3, the total combined number of transfer were 0,2,1.Conclusion1. Tumor inhibition rate of Combined Group 2 was 77.04%, has significant antitumor effect.2. Danshen injection combined with CTX. reduces the value of HIF-1a mRNA expression and serum VEGF concentration, inhibits tumor angiogenesis, thereby, enhance the inhibitory effect of CTX. in Lewis lung carcinoma.3. The expression of HIF-la mRNA and concentration of VEGF was a positive correlation between, concentration of Serum VEGF and microvessel density was a positive correlation.4. the CTX group can inhibite tumor angioggenesis better than combined group 2.5. Danshen injection increased tumor cell apoptosis of CTX, enhance their chemotherapy.6. Danshen injection can promote Lewis lung to Transfer.