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Before The Cancer Away For Prostate Cancer, Androgen Receptor Regulatory Factor Of Influence

Posted on:2013-06-14Degree:MasterType:Thesis
Country:ChinaCandidate:Y J YanFull Text:PDF
GTID:2244330371481627Subject:Integrative basis
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ObjectiveProstate cancer is the most common malignant tumor of the older men in the United States and Europe, our country has always been considered a low-incidence area of prostate cancer, however, as the living conditions and lifestyle changes, the incidence of prostate cancer showed a increasing trend year after year in China and the patient is also gradually getting younger and younger. Prostate cancer can be divided into two typesof androgen-dependent prostate cancer and androgen-independent prostate cancer. Early androgen-dependent prostate cancer is more sensitive to androgen deprivation therapy, However,after a period of12to18months,nearly all patients under the treatment of hormone deprivation therapies are progressing into androgen-dependent prostate cancer.Hormone therapy introduce no therapeutic actions in this stage, neither other therapies. A rapid progression can be observed in this stage and most patients stride to the end of the life.Chinese medicine performs well in the clinical practice in treating different Kinds of cancers and it is more and more employed in cancer treatment these years for the advantages of little side effect, multi-targets and multi functioning levels, focusing on comprehensive regulation of the body compared to the modern therapies.The QAX created by prof. Pei Wang,who is a Chinese oncologists,on the basis of his experiences in treating cancers, which is called the QAX with the function of nourishing the kidney and promoting blood circulation, The previous research in our laboratory indicated that the QAX should be used with cautions during the stage of androgen-dependent prostate cancer and it will give good performance on treating the disease during the androgen-independent stage.Besides, it can delay the disease progression from androgen-dependent stage into the androgen-independent.LNCaP cells, the classic androgen-dependent prostate cancer cells, are used in our program to test the effects of the QAX above in vitro, and We will further study on the basis of preliminary in vivo experiments to discuss the molecular mechanism of prostate cancer and to provide more theoretical basis for further clinical application.MethodsFirst, human androgen dependent cell line LNCaP cell was cultured.The cells with the1:1mixture of matrigel was inoculated in nude mice, preparing animal models of prostate cancer. After the modeling, nude mice bearing prostate cancer is the study objective and the QAX is intervening factors.When the tumor in nude mice grew to about45Omm3, randomly divided into the normal control group, the QAX group, the castration group and the castration+QAX group, the normal control group and the castration group were given saline after the castration, the QAX group and the castration+QAX group were given the QAX.Four weeks after the QAX intervention, all animals were sacrificed and removal of the tumor.Immunohistochemistry staining tumor for SRC-1and NCOR expression in tumor tissue. Using factors related to proliferation label AgNOR,examine it expressing characteristic in four groups.The methods of intragastric administration of equivalent dose decoction and surgical removal of the testicles were employed to prepare4groups of different rat serums, the Normal Control group, the QAX group, the Castration group and the Castration+QAX group. The serums described above are used to interfere the human androgen-dependent prostate cancer LNCaP cells to examine ARmRNA and protein (quantitative real time RT-PCR, Western blot), factors related to proliferation label Ki67and factors related to apoptosis label BCL-2、 Bax (quantitative real time RT-PCR), steroid receptor coactivator-l(SRC-l),nuclear receptor corepressors(NCOR)(quantitative real time RT-PCR).Results1. Using immunohistochemistry technique labeling SRC-1、 NCOR,study expressing characteristic of them in four groups of tumor tissue.the Normal Control group, the QAX group, the Castration group and the Castration+QAX group.Regarding expression of AR, it shows that high expression in tumor cells of the Castration group, AR in the Normal Control group is less than the Castration group:AR expression in the QAX group was less than the Normal Control group, AR in the Castration+QAX group was less than the QAX group.AR in the Castration group is less than the Castration+QAX group; AR expression in the Normal Control group was less than the QAX group.2. Using factors related to proliferation label AgNOR,examine it expressing characteristic in four groupshigh expression in tumor cells of the Normal Control group, AR in the QAX group is less than the Normal Control group the Castration+QAX group:AR expression in the Castration group was less than the Castration+QAX group.3. ARmRNA and proteinARmRNA and protein in the Normal Control group was less than the QAX group; AR expression in than the Castration+QAX group was less the Castration group.4. factors related to proliferation label Ki67and factors related to apoptosis label BCL-2、 BaxKi67and BCL-2in the QAX group is less than the Normal Control group the Castration+QAX group:Ki67and BCL-2expression in the Castration group was less than the Castration+QAX group.5. Steroid receptor coactivator-1(SRC-1), nuclear receptor corepressors(NCOR)SRC-1in the QAX group was less than the Normal Control group the Castration+QAX group:SRC-1expression in the Castration group was less than the Castration+QAX group.SRC-1in the QAX group was more than the Normal Control group the Castration+QAX group:SRC-1expression in the Castration group was more than the Castration+QAX group.Conclusion1. The QAX with the function of nourishing the kidnedy and Promoting blood circulation can reduce the SRC-1. AgNOR expression of the tumor tissue of the nude mice.2. The QAX with the function of nourishing the kidnedy and Promoting blood circulation can promote the AR、Ki67mRNA、 SRC-1mRNA、 Bcl-2mRNA,and reduce expression of NCORmRNA expression of LNCaP cells.3. Castration can suppress the AR mRNA and protein、 Ki67mRNA SRC-lmRNA、 Bcl-2mRNA expression of LNCaP cells, and promote the expression of NCOR mRNA.4. AR mRNA and protein、 Ki67mRNA、 SRC-lmRNA、 Bcl-2mRNA expression in the Castration and the QAX group was less than in the Castration group.
Keywords/Search Tags:Androgen Receptor (AR), Androgen-dependent Prostate cancer, Androgen-Independent Prostate cancer, LNCaP cells, nuclear receptorcorepressors, Prostate cancer, Qianaixiao, steroid receptorcoactivator-1
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