Clinical And Experimental Study Of Qingjin Desheng Tablets On The Elderly Patients With Advanced NSCLC

Objective:Primary lung bronchogenic carcinoma is one kind of the diseases threatening human being health and life gravely.In the 20th,the end of the century,lung cancer has become the leading cause of death in various types of carcinoma.The lung cancer morbidity increases with age,going up rapidly after 40-year old and reaches a peak until when being about 70-year old. Non-small cell lung cancer accounts for the vast majority of them.The issue of cancer in the elderly is of growing concern given the aging population. It is a particular issue in lung cancer,where the median age of patients is over 60.The issue of lung cancer treatment in the elderly has been the subject of recent comprehensive reviews.At present,the age alone has not been considered a significant contraindication factor to three treatments---surgery,radiotherapy, chemotherapy in the older patients with non-small lung cancer.However,as the prevalence of dysfunction and comorbidity increase with age,the results of three main treatments are not satisfactory.Elderly tolerance to treatment and to maintain a better quality of life is of the primary issues that must be given attention.In china,traditional Chinese medicine plays a very important role in treating elderly patients with NSCLC.As one of five main methods in treating lung cancer,TCM can stabilize the tumor,regulate body functions,increase immunity,relieve the clinical symptoms,increase appetite,reduce the side effects of radiotherapy and chemotherapy,improve the quality of life and prolong survival with a unique effect and so on.TCM have unique advantages in treating the elderly patient with advanced NSCLC.Metastasis is one of the fundamental biology characters for the malignant tumor and it is the most important factor leading to the cure failure and patient death.With the cell biology and the molecular biology development, the new methods have been approached,which has provided the new thoughts and methods for the anticancer metastasis of traditional Chinese medicine studies. Research for prevent cancer from metastasis in TCM is still in its infancy, especially for traditional Chinese medicine-induced anoikis studies.This study will investigate the clinical efficacy of Qingjin Desheng Tablets on behalf of Yi-qi-chu-tan principles on elderly patients with advanced NSCLC and explore a reasonal,standard and economic way for the treatment of the elder lung cancer.In the field of the experiment,the thesis intends to study the effects of Qingjin Desheng Tablets on anoikis resistance in human lung cancer cell—AS49 and investigate the expression of signaling protein phosphor-AKT.Methods:Clinical part:48 elderly patients with NSCLC were selected and divided into 2 groups randomly:24 cases of treatment group and 24 cases control group. There is no significant difference in sex,age,pathology,differentiation grade,weight,performance states and the treatment before between the treatment group and the control group(P> 0.05).The two groups accepted the same supporting treatment.Meanwhile,the treated group was treated with Qingjin Desheng Tablets;the control group was treated with An-kang-xin capsule,last 60 days.The therapeutic efficiency and adverse effect of the two groups were evaluated after curing 60 days,then estimated it clinical effect and safety.Experiment part:We cultivated adenocarcinoma cell-AS49 in suspension state by using poly-HEMA and simulate the state of anoikis of cancer cells in vivo.The cell apoptosis and period were measured by FCM after adenocarcinoma cell-A549 treated with serum containing Qingjin Desheng Tablets.The expression of P-akt in each group of cells was detected by Western-blot.Results:Clinical part:(1) No cases reached CR or PR equally in the two groups. The treatment group and control group tumors reached a stable rate of 79.17% and 75%respectively.Although there being no notable difference,it had showed certain advantage of stabilizing the tumor with traditional Chinese medicine treatment.(2) Both treatment group and control group were no improvement in clinic symptoms.In treatment group,effective rate was 54.17%,stable rate was 29.17%and invalid rate was 16.67%.In control group effective rate was 50.00%,stable rate was 33.33%and invalid rate was 16.67%.There were no significant difference between two groups(P>0.05 ).Through further observation,we found that Qingjin Desheng Tablets in alleviating the symptoms of chest pain and dry mouth,were better than An-kang-xin capsule.(3) After treatment,there were no striking difference between two groups in KPS (P >0.05)(4) There was no deterioration of body weight in two groups.The patients with stable weight were 83.33%and 87.50%respectively in treatment group and control group.The difference between the two groups was not significant(P> 0.05).(5) There were no significant difference to CEA and ESR in two groups before observation.After treatment,both CEA and ESR in two groups had obvious gone down.There were striking difference between two groups in ESR(P < 0.01),which showed that state of illness was to tend to stability.(6) There were no obvious blood toxicity and damage to liver and kidney functions after the treatment.(7) No serious adverse events and serious adverse reactions was found in clinical studies.According to the results of this clinical study,we found whether Qing-jin-de-sheng tablet or An-kang-xin capsule in treat elderly patients with advanced non-small cell lung cancer could stabilize tumor,relieve the clinical symptoms,reduce tumor marker CEA and maintain the patient's condition etc.There were no significant toxicity,and better reflects the advantage of TCM.Experiment part:(1) The cell apoptosis in every serum containing Qingjin Desheng Tablets was higher than blank space serum.With the serum containing Chinese medicine going up with the concentration,the apoptosis rate increased gradually.Chemotherapy drug-cisplatin group achieved the highest rate of apoptosis.(2) P-akt expression in the platinum group was lowest,32.It showed a significant reduces comparable with the blank blood serum group and the low monitoring group P-akt expression in the high dose group was 59,which showed a significant reduces comparable with the blank blood serum group and the low monitoring group too(p<0.05 ).Relative expression of P-akt among the monitoring team(20%),the low dose(10%) and the blank blood serum group were 69,127 and 122 respectively.The serum containing traditional Chinese medicine group,along with density gradual reduction,the P-akt expression had the tendency of increase gradually. Combined with previous research,we concluded that Qingjin Desheng tablets have the function of leading A549 cells in suspension state to death.The mechanism may be for traditional Chinese medicine containing serum by blocking the anti-apoptotic gene bcl-2's role.Qingjin Desheng Tablets exerted the anti-tumor action thought inhibiting the P-akt activation and expression, which reduced the telomerase activity and modulating the expression of bcl-2 and bax2 protein.