Observation Of Qilian Mixture On The Treatment Of Patients With Advanced NSCLC Chemotherapy And Study On The Anti-Tumor And Immune Effects Of Formononetin

Objective: 1.By observing the clinical effect of the Qilian Mixture combined with chemotherapy on stage IIIB and IV NSCLC of lung qi deficiency type patients and its influence on immune function,this paper expounds its unique advantages in the clinical treatment of patients with non-small cell lung cancer and provides the new scientific basis for the treatment of lung cancer with traditional Chinese medicine.2.The representative drug Huangqi of Yiqi Fuzheng in Qilian Mixture was selected,and its effective monomer component,formononetin,was taken as the research object to explore its anti-tumor immune response,so as to open up new ideas for the treatment of NSCLC.Methods: 1.Clinical research: Through randomized controlled design,patients who were treated in Qingdao Haici Medical Group from October2020 to October 2022 were selected as the observation objects and 70 patients with stage IIIB and IV NSCLC who met the inclusion criteria and were diagnosed as lung qi deficiency type were selected.The data is randomly divided into a control group(chemotherapy alone)and a treatment group(combined with traditional Chinese medicine),35 cases each.The baseline data,Karnofsky score,TCM syndrome score,serum carcinoembryonic antigen CEA,cytokeratin-19-fragment CYFRA21-1,and T lymphocyte subsets were compared between the two groups.2.Experimental study: 40 C57 BL / 6 male mice were randomly divided into 5 groups(8 groups): normal group,qi deficiency tumor group,FO-H(high concentration group of formononetin,100 mg/kg/d)group,FO-M(medium concentration group of formononetin,50mg/kg/d)group,FO-L(low concentration group of formononetin,25mg/kg /d)group.Apart from the normal group,four other groups smoked for 21 days to induce lung qi deficiency model.After successful modeling,Lewis lung cancer cells were injected to induce a tumor model.After 15 days of continuous administration,The abnormal behavior of the mice was observed and recorded over time and measured the mice’s body weight and tumor volume every three days.15 days later,the mice were sacrificed,and the transplanted tumor,spleen,thymus,liver,and kidney tissues were dissected,and the spleen and thymus indexes were calculated.Hematoxylin-eosin staining was used to evaluate the changes in liver and kidney toxicity and tumor morphology in mice.The proportion of regulatory T cells,helper T cells,killer T cells,and B cells were detected by flow cytometry.The expression of PI3 K,AKT,and m TOR protein was detected by RT-PCR.Results:1.Clinical research: A total of 70 patients were recruited for this study,and 60 patients completed the study(30 in the treatment group and 30 in the control group).There was no meaningful difference in general baseline data(gender,age,stage,pathological type,etc.)between the two groups before treatment(P > 0.05).Before treatment,There was no significant difference in TCM syndrome efficacy score,KPS score,tumor markers(CEA,CYFRA21-1),and T lymphocyte subsets between the two groups(P > 0.05).The TCM syndrome score,KPS score,KPS function,tumor markers(CEA,CYFRA21-1),and T lymphocyte subsets were significant differences between the two groups after treatment(P < 0.01),and the curative effect of TCM syndrome was statistically significant(P < 0.05).There were significant differences in TCM syndrome scores,tumor markers(CEA,CYFRA21-1),and T lymphocyte subsets before and after treatment in the treatment group(P < 0.01).The KPS score P = 0.022 < 0.05 was statistically significant.The TCM syndrome score ratio of the control group before and after treatment was statistically significant(P < 0.05).There were significant differences in tumor markers(CEA,CYFRA21-1),serum T cell subsets CD4 + and CD8 + cell percentages(P < 0.01).KPS score and serum T cell subsets CD4 + / CD8 + levels were not statistically significant(P < 0.05).2.Experimental study: In the LLC transplanted tumor mouse model,after the intervention of formononetin,the tumor volume growth and tumor mass of each group were significantly lower than those of the qi deficiency tumor-bearing group(P < 0.01).Compared with the Qideficiency tumor-bearing group,the density of tumor cells in the FO-H,FO-M,and FO-L groups decreased,the necrotic area increased,and the arrangement of tumor cells was relatively disordered.No obvious lesions were found in liver and kidney tissues;compared with the Qi deficiency tumor-bearing group,the proportion of B cells(CD3-,CD49 b +),killer T cells(CD3 +,CD8 +)and helper T cells(CD3 +,CD4 +)in the low concentration group of formononetin increased,the difference was statistically significant(P < 0.05),and the high concentration group and the medium concentration group had significant statistical difference(P < 0.01).The proportion of regulatory T cells(Treg)(CD3 +,CD4 +,CD25 +,Foxp3 +)in the low and medium concentration groups of formononetin was higher than that in the Qi deficiency tumorbearing group(P < 0.05).The increase in the high-concentration group was statistically significant(P < 0.01).In the high-concentration group and the low-concentration group,the ratio of CD4 + / CD8 + was meaningfully higher than that in the Qi deficiency tumor group(P <0.01).The expression levels of PI3 K,AKT,and m TOR were downregulated after administration(P < 0.01).Conclusion:1.Compared with chemotherapy alone,Qilian Mixture combined with AP and DP chemotherapy regimen can improve the quality of life of patients with advanced NSCLC of lung qi deficiency type,improve the immune function of the body,reduce the level of tumor markers,improve the physical condition of patients and some TCM symptom scores;2.Experiments have shown that formononetin can slow down the growth rate of implanted tumors in non-small cell lung cancer mice with lung qi deficiency,inhibit the growth and diffusion of tumor cells,improve the quality of life of Lewis lung cancer-bearing mice,and increase the spleen and thymus index.Increase the proportion of helper cells(CD3 +,CD4 +),killer cells(CD3 +,CD8 +),regulatory T cells(Treg)(CD3 +,CD4 +,CD25 +,Foxp3 +),and B cells(CD3-,CD49 b +)and the ratio of CD4 + / CD8 +(P < 0.05),reduce the transcriptional activity of PI3 K / Akt / m TOR signaling pathway,improve the immune status of the body,in order to obtain a better immune anti-tumor effect.