Clinical Efficacy Observation And Mechanism Study Of Zhengdekang Capsule In The Treatment Of Advanced Non-small Cell Lung Cance

Objective:According to the latest statistics from authoritative international oncology journals,lung cancer has the highest morbidity and mortality among all cancers.As early as in the late 1960s,professor Jiaxiang Liu,a master of Chinese medicine,put forward the academic thought of "fuzheng cure cancer",developed Zheng de kang Capsule(Zheng de kang),carried out relevant clinical and experimental research,and won the third prize of Science and Technology in Shanghai in 1997.Based on the previous studies of Zheng de kang,this study explored the preliminary clinical efficacy of Zheng de kang through randomized and controlled clinical studies and in vivo and in vitro experimental studies,and revealed the anti-metastasis mechanism of Zheng de kang,so as to provide the basis of "fuzheng Cure cancer" for the treatment of lung cancer metastasis.Method:Clinical research adopts prospective,randomized and controlled method,a total of 45 cases of TCM syndrome differentiation of qi and Yin deficiency type of advanced non-small cell lung cancer patients were collected from 4 branch centers from November 2019 to September 2020,randomly assigned to treatment group(given Zheng de kang plus chemotherapy)and control group(given chemotherapy alone),regular follow-up was conducted after 2 cycles of treatment(1 cycle is 21-28 days).Evaluate the patient’s quality of life,TCM symptoms,physical status,objective remission rate,tumor index,immune index changes,and detect circulating tumor cells(CTC),select appropriate statistical methods for statistical analysis and draw conclusions.In the experimental study,mouse lung cancer cells(LLC)were injected into the tail vein to construct a mouse lung metastasis model,and detected the expression of EMT-related protein,the number of immune cells and cytokines in tumorbearing lung tissues of mice,meanwhile,the alcohol extract of Zheng de kang was used in two lung cancer cells(LLC and H1299).Colony formation,flow cytometry,transwell,western blot,F-actin staining were used to explore the anti-metastasis mechanism of Zheng de kang capsules in vivo and in vitro.Result:1.Clinical research:(1)After treatment,the symptoms of fatigue,constipation,and dyspnea were significant in the control group,and the difference was statistically significant(P<0.05).The physical function,role function,and social function decreased significantly,and the difference was statistically significant(P<0.05).Compared with the two groups,the fatigue score of the treatment group was lower than that of the control group(P<0.05),and the overall health level was higher than the control group(P<0.05).After treatment,the KPS score of the treatment group was better than the control group(P<0.05).(2)Zheng de kang can reduce CTC steadily and lastingly,and improve the reflex phenomenon during chemotherapy.There was weak negative correlation between CTC and disease progression(PD)and disease remission(PR).The objective remission rate and disease control rate of the treatment group were 13.6%and 95.4%,respectively.The objective remission rate and disease control rate of the control group were 13.0%and 69.5%,respectively.There was a significant difference in the disease control rate between the two groups(P=0.000).These indicate that Zheng de kang could stabilize the lesion and control the disease progression.(3)CTC is positively correlated with carcinoembryonic antigen(CEA),cytokeratin 19 fragment(CYFRA211),helper T cells(CD4+),and CTC is related to squamous cell carcinoma antigen(SccAg)and carbohydrate antigen 125(CA125).There is a negative correlation between T lymphocytes(CD3+)and cytotoxic T cells(CD8+).There is no correlation between CTC and natural killer cells(NK cells)and CD4+/CD8+.These suggest that CTC can be an important clinical reference index to guide the clinical diagnosis and treatment of lung cancer.2.Experimental research:(1)In vivo animal experiments showed that compared with the control group(administered with normal saline),the number of lung metastases in the treated group(administered by Zheng de kang)was statistically different(P<0.01).There was no significant decrease in body weight,and Zheng de kang could prolong the survival time of mice to a certain extent;Compared with the control group,there was a significant statistical difference in M2 tumor-associated macrophages(TAMs)in the lung tissue of the treatment group(P<0.01).CD4+,CD8+T cells,and dendritic cells(DC)increased,and there were significant statistical differences(CD4+T cell:P<0.01,CD8+T cell:P<0.001,DC:P<0.001).(2)In vitro cell experiments showed that Zheng de kang extract can inhibit the proliferation of LLC and H1299 cells,promote cell apoptosis,and up-regulate the expression of E-cadherin and down-regulate the expression of protein(Vimentin)and transcription factors(snail,slug)in epithelial-mesenchymal transition(EMT).The formation of filopodia and the extension and expansion of lamellipodia are inhibited.Conclusion:1.Clinical research:(1)Zheng de kang can relieve fatigue,anorexia,constipation and other clinical symptoms caused by chemotherapy,and improve the quality of life of patients without increasing the side effects of chemotherapy.It has good safety and effectiveness.(2)Zheng de kang plus chemotherapy can stabilize local lesions and control disease progression;Zheng de kang can reduce CTC steadily and lastingly.There is no reversal of CTC in the course of chemotherapy alone.CTC is related to disease control rate(DCR)and objective response rate(ORR),indicating that Zheng de kang can not only stabilize the lesions,improve the quality of life,and also have anti-tumor metastasis effects.(3)There is a correlation between CTC and tumor markers and immune indicators,which can be used as important clinical reference indicators to guide the clinical diagnosis and treatment of lung cancer.2.Experimental research:(1)Zheng de kang significantly inhibits the number of lung metastases in mice,and its anti-metastatic mechanism may be related to regulating the expression of EMTrelated proteins.(2)Zheng de kang can increase immune promoting cells and suppress immunosuppressive cells to regulating the immune response of mice.(3)Zheng de kang can inhibit the invasion ability of lung cancer cells in vitro,inhibit lung cancer cell proliferation,induce lung cancer cell apoptosis,regulate the expression of EMT-related proteins,affect the formation of F-actin cytoskeleton,and thereby inhibit lung cancer metastasis.