| AIM:To optimize the extraction technique of Xianyu Decoction.To observe the inhibitory effects of Xianyu Decoction(XYD)and Cisplatin(CDDP)on tumor growth,immunoregulation,the side effect on the mice blood system,cell cycle and to investigate its effect on apoptosis of tumor cells,and to investigate its mechanism.To evaluate the effect and adverse reactions of combined ehemotherapy and Xianyu Decoction in the treatment of medium or late stage none-small cell lung cancer(NSCLC).METHODS:1.Extraction technique:Orthogonal design was used to observe the condition of water extraction,with the yield of total flavonoids and total glycosides as the observation indexes.2.Empirical experiment:The Lewis lung cancer cells were thawed, then inoculated to BALB/C mice.Sixty mices were divided into six groups equally,including model group,low dose of Xianyu decoction group(1.092g·ml-1),middle dose of Xianyu decoction group(2.184g·ml-1),high dose of Xianyu decoction group(4.368 g·ml-1),CDDP group(3mg/kg),CDDP/Xianyu decoction group(4.368 g·ml-1).Afler15 days,the mices were put to death by cervical vertebra dislocation.The tumors and spleens were separated,weighedand then calculated the average weight and the inhibition rate of the tumors and spleen index for each group.blood picturewas analsized by globulimeter. The Lewis lung cancer cells were thawed and cultured.Cells were divided into six groups: model group,low dose of Xianyu decoction group(1.092 g·ml-11),middle dose of Xianyu decoction group(2.184 g·ml-1),high dose of Xianyu decoction group(4.368 g·ml-1),CDDP group(2u g·ml-1),CDDP/ Xianyu decoction group(4.368 g·ml-1).After a 48-hour treatment,the cells of each group were collected and the flowing measures were carried out. Cells proliferation was measured by thiazolyl blue(MTT)assay;Cell cyclin distribution were determined by flow cytometre.Cell apoptosis was determined by TUNEL assa.3. Clinical research:90 patients with stageⅢb-ⅣNSCLC were divided randomly into three groups,namely,A,B and C.In group A,30 patients were treated with Xianyu Decoction alone.In group B(as a control group),30 patients were treated with chemotherapy alone.In group C,30 patients were treated with chemotherapy combined with Xianyu Deeoetion. The effect and adverse reactions of the three groups,including the changes of tumors,the main symptoms of NSCLC,quality of life,body weight,immunity and side-effect,were evaluated after one course of treatment.RESULTS:1.Extraction technique:The factors of solvent dosage and extracting times were directly related to the various indexes.The optimal technique was determined as follows:water dosage,15 fold of water;extracting time,30minutes per each time; extracting times,3 times;immersion time,15minutes.2.Empirical experiment:①.tumor's weight of each of thetherapeutic groups was lighter than that of the model group(p<0.01).In theChinese Medicine groups,the more the dosage grew,the lighter the tumor's weight became and the higher the inhibition rate of the tumor was.Inhibitory rates of CDDP/Xianyu decoction group was 68.98%,significant differenet with CDDP group.②Compared with model group,spleen index in tumor-bear mice was reduced significantly at middle and high dose(P<0.01).spleen index of CDDP/Xianyu decoction group was incresed,significant differenet with CDDP/Xianyu decoction group(P<0.01).③The number of WBC,RBC,Hb have no significant differenet at all dose of Xianyu decoction.,but were decresed in CDDP group.The number of WBC in mice was incresed,significant differenet with CDDP group(P<0.05).④apoptotic and necrosis area was incresed in each of thetherapeutic groups.⑤Compared with control group,MTT values of cells were decreased(P<0.01),the percentage of S stage cells was downregulated and the percentage of G0/G1 stage cells was upregulated by flow eytometry(P<0.01 or P<0.05),apoptotic cell number was incresed in each of thetherapeutic groups.Compared with CDDP group,CDDP/Xianyu decoction group had significant differenet(P<0.01).3. Clinical research:The complete and partial remission rate(CR+PR)of Group C(46.67%) was higher than GroupB(26.67%0),but have no significant difference between them(P>0.05).The complete and partial remission rate of Group A(3.33%)was lower than GroupB and Group C(P<0.01);The stable rate(CR+PR+SD)of Group C(83.33%)was the highest but had no significant difference comparing with Group B(60.00%)(P>0.05),The stable rate of GroupA(70.00%)was higher than the Group B,but had no significant differenee(P>0.05).The Group A had a better effeet in the remission of symptoms such as cough,fever,polypnea,debility than Group B(P<0.05 or P<0.01),there was no significant difference between Group A and Group B in the remission of symptoms such as hemoptysis and anorexia pectoralgia(P>0.05).The Group C had a better effect in the remission of symptoms such as cough,hemoptysis,fever,polypnea and debility than Group B(P<0.05),there was no significant difference between Group A and Group C in the remission of symptoms such as peetoralgia and anorexia(P<0.05).The Kamofsky scores in Group A and Group C increas more than that in Group B after a course of treatment(P<0.05 or P<0.01).The three groups could increase the body weight of patients more or less,by comparison,Group A and Group C increase more than Group B(P<0.05 or P<0.01). Moreover,Xianyu Decoction could increase the percentage of national kill cell(NKC)and LBT in GroupA and Group C after treatment,especially GroupA increased obviously(P<0.01).Group A and Group C increase significantly the percentage of NKC and LBT than Group B after treatment(P<0.01).In Group A and Group C,Xianyu Decoction could increase CD4+,CD4+/CD8+.Group A and C showed significant difference with group B.However there was no statistically significant difference between A and C, it showed that Xianyu Decoction could enhence the human immunity ability.Xianyu Decoction had no severe adverse reactions.The rate of adverse reactions in Group C were lower than that in Group B,especially in the field of the system of hematology,aspartate aminotransferase(AST),vomit,blood urea nitrogen(BUN), ereatinine(CREA),heart rate,hypersusceptibility,hair,peripheral nerve and skin,there were significant difference(P<0.05).CONCLUSIONS:1.Xianyu decoction remarkably inhibited the growth of Lewis lung carcinoma in mice,and the effect might be associated with inhabition of cell cycle and induction of apoptosis on cancer cells.2.Xianyu decoction can elevate the immune function of Lewis lung carcinoma in mice,and has no side effection for the mice blood system.Xian Yu Tang can relieve the toxis and side-effect of cisplatin.The side-effect of Xianyu Decoction was less.It could stabilize the tumor,alleviate the symtoms of the medium or late NSCLC patients,improve the qualityof life,increases the body weight, improve the immunity.Combined with chemotherapy,Xianyu Decoction could enhane the efficincy and reduce the side-effect of chemotherapy. |