| According to the theory of traditional Chinese medicine,the growth of tumor is closely linked to stagnation of blood. And blood stasis also can promote tumor metastasis.Therefore,hemorheologic agents are used to threat tumor extensively.However,there are some modern experimental findings indicating that these drugs can promote tumor metastasis.It makes a part of doctors immune to use these drugs.What functions do hemorheologic agents have? Is it synergism or antagonism when Chem drugs and hemorheologic agents are used together? What is the mechanism of action? It is difficult to draw a objective and precise conclusion resulting from kinds of factors such as different varieties, times,doses,matches and so on.The earlier studies of my supervisor indicated that the blood activating drugs can perform not only depressant effect but also promotion for tumor metastasis since different conditions.It is obvious that the mechanism of actions are very complex.It needs us to do more research..This study was carried out on the base of the earlier research of my supervisor,and was supported by NSFC.We carried out a small sample clinical reseach on NSCLC patients,observing the changes of syndrome of blood stasis after chemotherapy.The results showed that chemotherapy aggravated stagnation of blood. Experiments in vivo were designed on the base of considering various factors referring above. We chosed four kinds of typical hemorheologic agents named Chuanxiong,Jixueteng,Sumu and Shuizhi.These drugs were used for mice planted Lewis lung carcinoma when it was in different stages.After the difference comparison studying on the inhibiting rate of lung metastasis in Lewis lung carcinoma model of mice. As a result, Sumu did the best work.It effected the growth and metastasis of tumor greatest.We chose Sumu for further study which aimed to illuminate the mechanism of action.In animal experiment, the positive rate of CD44 in the tumor cells were measured by a flow cytometer and sP-selectin were measured by a ELISA kit in three phases.Meanwhile, The expression of CK18 and CK19mRNA in marrow of mice were measured by Real-time PCR. Compared to NS group,other groups decreased tumor weight,lung metastatic foci,the positive rate of CD44 as well as the concentration of sP-selectin. The expression of CK18 and CK19mRNA was weaker than the NS group.The results indicated that the mechanism of inhibiting metastasis maybe related with degrading the expression of CD44 and sP-selectin.The experiment indicated the mechanism of inhibiting metastasis on cell adhesion.Meanwhile,it justified the inhibiting metastasis action by testing micrometastasis indexes.1 The main research conclusions1.1 Clinical Observation on the change of Blood Stasis Syndrome in Patients with NSCLC after chemotherapy60 advanced NSCLC patients before and after two cycles of chemotherapy were classified according to all evidence-based standards for their classification type, the results showed:after 2 cycles of chemotherapy, blood stasis syndrome significantly increased in proportion (P<0.01).Phlegm card, Qi stagnation, heat and toxic syndrome declined in proportion,while qi deficiency, blood deficiency, yin deficiency and yang deficiency ratio had upward trend, but had not statistically significance (P> 0.05). APTT, FIB, D-â…¡dimer test values had significant differences (P<0.01),and MCV test values had statistically significance (P<0.05).1.2 Effects of four kinds of hemorheologic agents on C57BL/6 mice transplanted with Lewis lung carcinoma in different phases.The C57BL/6 mice transplanted with Lewis lung carcinoma were intervened by four kinds of hemorheologic agents(Chuanxiong,Jixueteng,Sumu,Shuizhi).We observed the inhibiting rate on tumor growth and metastasis in three phases.We found that:â‘ In terms of tumor weight,on 5th day, there was significant difference between Sumu group and NS group,as well as Jixueteng group and NS group. On 10th day,there was a significant difference between Sumu group and NS group, between Jixueteng group and NS group, as well as between Shuizhi group and NS group. On 21th day,there was no significant difference between medication group and NS group.â‘¡In terms of metastasis foci,there was a significant difference between Chuanxiong group and NS group, as well as between Sumu group and NS group.â‘¢The action of these drugs to inhibit tumor growth and metastasis was weaker and weaker as the stage advanced. Compared to three other drugs,Sumu had better effect on decreasing tumor growth and metastasis,so we chose Sumu for further research. 1.3 Effects of Sumu and Sumu combined chemotherapy on tumor growth,metastasis of C57BL/6 mice transplanted with Lewis lung carcinoma in different phasesBy further observing tumor weight,metastasis foci,meanwhile expression of CD44 tested by flow cytometry,sP-selectin tested by ELISA,CK18mRNA and CK19mRNA tested by Real-time PCR in different groups.Results:Sumu and Sumu adding CTX can inhibit the tumor growth and metastasis. The mechanism of inhibiting metastasis maybe related with degrading the expression of CD44 and sP-selectin.2 The new ideas and characteristics of the researchThere are several new ideas and characteristics in this research:first of all, observed the effects of hemorheologic agents on tumor growth and metastasis of mice transplanted with Lewis lung carcinoma and researched the mechanism of the action in three phases.We designed animal experiment according the results of clinical observations.It regarded a disease as a continous variable course in order to choose the best time to threat. Further more,combined hemorheologic agents and chems drug together.Interactions were researched.We obtained the experiment rationale for drug combination.Last,when we observed the tumor metastasis, not only used microscope to observe the metastasis foci, but also resorted to Real-time PCR to test micrometastasis.It combined macroscopic and microcosmic testing together.It made the results accurate and object. |
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