Study Of Xiaoyan Granules Combined With Chemotherapy On MDSC-NKT Immunoregulating In Patients With Advanced Non-small Cell Lung Cancer And Its Mechanism

1 Purpose:Exploring the effecacy and mechanism of Xiaoyan granule combined with chemotherapy in the treatment of advanced non-small cell lung cancer through clinical observation and experimental research.Clinical observation is to determine whether Xiaoyan granule has the effects of enhancing immune function and improving quality of life.Animal experiments is to establish a Lewis lung cancer mouse model and detect the level of MDSCs and NKT cells in the spleen of the model mice and the expression of cytokines VEGF,TGF-?and IL-6 in the blood of the model mice in order to reveal regulatory mechanism of MDSC-mediated immunosuppression and explore possible signal pathways.2.Method2.1 Clinical researchThirty patients with advanced non-small cell lung cancer were selected according to the Inclusion and exclusion criteria and divided into two groups at a ratio of 1:1.The control group 15 cases were given platinum-containing dual-drug chemotherapy and routine treatment,and the treatment group 15 cases were given Xiaoyan granules 9g Bid combined with platinum Dual-drug chemotherapy and routine treatment,the two groups of patients received at least 2 cycles of treatment.The main observation indicators were peripheral blood MDSCs and their subtypes:expression levels of CD15^+/CD33/CD11b⁺/CD14,and the number of T cell subsets.The secondary observation indicators were disease control rate,objective remission rate,quality of life and occurrence of adverse reactions rate.2.2 Experimental researchThirty mice were randomly divided into 5 groups?6 mice in each group?:blank control group,tumor-bearing control group,cyclophosphamide single drug group,Xiaoyan decoction single drug group and cyclophosphamide combined Xiaoyan decoction group.Except for the blank control group,Lewis lung cancer mouse models were established in all other groups.When the tumor volume reached about 50mm³,the blank control group and the tumor-bearing control group were given saline and the experimental drug group was given corresponding concentrations of drugs.Gavage once a day for 7 days.Observing the general living conditions of mice such as diet,hair,activity,mental state during the gavage.The mice were sacrificed and the tumor tissue was stripped after 7 days,calculating the tumor inhibition rate and weighting the spleen weight to calculate the spleen index.Using flow cytometry to detect the level of MDSC and NKT cells in the spleen of Lewis lung cancer mice and using ELISA to detect the changes of VEGF,TGF-?and IL-6 in peripheral blood of mice.3.Results.3.1 Clinical researchIn terms of immune function,Xiaoyan granule combined with chemotherapy can significantly reduce the level of G-MDSC in peripheral blood of patients with non-small cell lung cancer;for T cell subsets,Xiaoyan granule combined with chemotherapy can increase the number of CD3⁺/CD4⁺cells,compared with the control group The difference is statistically significant,showing an advantage in reducing the number of CD3⁺/CD8⁺cells and increasing the ratio of CD4⁺/CD8⁺,but there is no statistical difference;in terms of stabilizing the tumor body and inhibiting tumor growth,the disease control rate and objective response rate between the two groups Similar to the treatment group?85.7%,21.4%?and the control group?76.9%,18.1%?;the combined medication group and the chemotherapy alone group can effectively reduce the CEA and CYFRA21-1 levels but there is no significant differences.In terms of improving the quality of life and adverse effects,the Xiaoyan granule combined chemotherapy group has an advantage over the control group in improving the patient's quality of life,but there is no significant difference.The Xiaoyan granule combined chemotherapy reduces the patient's fatigue and lack of appetite and the incidence of leukopenia,thrombocytopenia,and hemoglobin,but no significant difference was seen between the two groups.3.2 Experimental researchXiaoyan decoction combined with chemotherapy can inhibit the tumor growth of Lewis lung cancer mice and reduce the spleen index of mice.Xiaoyan decoction and cyclophosphamide can reduce the MDSC level in the spleen of tumor-bearing mice,and the combined application of the two has a synergistic effect.Xiaoyan decoction can increase the level of NKT cells in the spleen of tumor-bearing mice.Both Xiaoyan decoction and cyclophosphamide can inhibit the expression of IL-6,TGF-?and VEGF in peripheral blood of Lewis lung cancer mice,and the joint application of the two has a synergy effect on inhibiting the expression of VEGF.4 ConclusionXiaoyan granule combined with chemotherapy in the treatment of patients with advanced non-small cell lung cancer has the effect of improving the immune function of the patient and has the advantages of stabilizing the tumor body,reducing the incidence of adverse reactions of chemotherapy,and improving the patients'qualiy of life.The improvement of immune function is mainly reflected in the reduction of MDSCs cells.The mechanism may be related to increasing the level of NKT cells,reducing the expression of TGF-?,VEGF,IL-6,and initiating the JAK2/STAT3 pathway.