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Study Of The Effect And Mechanisms Of Fuzhengjiedu Therapy On Chemotherapy’s Synergy And Attenuation By NF-κB Anti-Apoptotic Signaling Pathway

Posted on:2016-08-13Degree:DoctorType:Dissertation
Country:ChinaCandidate:S LiuFull Text:PDF
GTID:1224330464455969Subject:Integrative Medicine
Abstract/Summary:PDF Full Text Request
Lung cancer is a very dangerous disease that affects many people and their families.Its incidence and mortality ranks first. Non-small-cell lung cancer (NSCLC) accounts for Majority. Chemotherapy is the main treatment for NSCLC, but resistance to chemotherapeutic agents is a major problem in oncology, which limits the effectiveness of anti-cancer drugs.The effective way to improve the therapeutic efficacy is to reduce the resistance to chemotherapy. A variety of factors contribute to drug resistance.The abnormal apoptosisisits inherent characteristics among them. The apoptosis of cancer cells was inhibited, resulting in the decrease of cell death, causing resistance to chemotherapy. Traditional Chinese medicine combined with chemotherapy can improve therapeutic efficacy, reduce side effect. In order to verify the clinical effect and to explore its mechanism of this action, we design the clinical observation and animal experiment by using traditional Chinese medicine’ s ’Fuzheng Jiedu’ method (Kang Ai injection) combined with chemotherapy.Objectives:The purpose of this study is to investigate the clinical effect of ’Fuzheng Jiedu’ Method Combined with chemotherapy and its mechanism of action. Methods:1. We conducted a multi-center prospective randomized controlled clinical trial. 72 cases of non-small-cell lung cancer patients were divided into chemotherapy group and traditional Chinese medicine (Kang Ai)+ chemotherapy group. The tumor size and side efect were evaluated before and after treatment.2. We established the C57 mice Lewis lung cancer model in situ (Orthotopic Xenograft Model), mice were given’Fuzheng Jiedu’ Chinese medicine and chemotherapy intervention. We used vivo imaging system to observe the change of tumor size, and recorded mouse body weight and survival time. Mice were sacrificed after intervention, tumor and spleen weight were recored. The serum levels of cytokines were detected by using flow cytometry.Western Blot method was used to detect the protein expression of NF-kB p65, Bcl-2, the Bcl-X1 and the apoptosis of tumor cells were evaluated by Tunel method.Results:1.Our clinical research showed that traditional Chinese medicine (Kang Ai)+ chemotherapy group can significantly improve the clinical benefit rate (P<0.05) compared with the other groups.At the same time, KPS score were also improved significantly in this group (P<0.05).Traditional Chinese medicine combined with chemotherapy group had obvious effect on adverse reaction of chemotherapy, including induced nausea, vomiting and loss of appetite (P<0.05). This group also can reduce the inhibitory effect of chemotherapeutic drugs on bone marrow and liver and kidney function damage (P<0.05).2. Our experiment study showed that traditional Chinese medicine (Kang Ai)+ chemotherapy group can reduce the inflammatory cytokines (P<0.05) compared with the other groups. The expression of NF-kB, anti-apoptotic protein Bcl-2 and Bcl-Xl were lower in the treatment group. The apoptosis of lung cancer cells of this group of mice increased significantly (P<0.05).The tumor size of this group is the smallest in the course of the mid-term (P<0.05). In this group, the tumor weight was the smallest in the course of the later (P<0.05), weight loss is the least in the treatment process (P<0.05), but also has the highest survival rates (P<0.05).Conclusions:1. Traditional Chinese medicine ’Fuzheng Jiedu’ method combined with chemotherapy, can increase efficacy and also reduce side effect of chemotherapy in clinic.2. Traditional Chinese medicine ’Fuzheng Jiedu’ method combined with chemotherapy can increase the efficacy, reduce toxicity effect in animal experiments. Traditional Chinese medicine ’Fuzheng Jiedu’ method combined with chemotherapy play this action by reducing cytokine levels of serum inflammation, NF-kB activation, thereby blocking "NF-kB anti apoptotic pathways" The increased apoptosis of lung cancer cells may contribute to improve the efficacy of chemotherapy.
Keywords/Search Tags:Non-small-cell Iung cancer, traditional Chinese Medicine, Fuzheng Jiedu method, Increase the efficacy, Reduce side effect, To reduce the resistance to chemotherapy, Anti apoptosis, NF-kB, Bcl-2, Bcl-XI
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