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Kidney Cancer eliminate delay before stasis from androgen-dependent prostate cancer to non- dependent conversion of experimental study

Author: YuXueFei
Tutor: HaoZuo
School: Beijing University of Traditional Chinese Medicine
Course: Chinese and Western medicine combined with the basis
Keywords: Kidney and stasis Eliminate precancerous Hormone-dependent prostate cancer Androgen-independent prostate cancer Androgen receptor PI3K-AKT-PTEN
CLC: R273
Type: Master's thesis
Year: 2011
Downloads: 64
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Abstract


Objective In recent years, the incidence of prostate cancer in China has grown rapidly, has been living in our male genitourinary malignancies third. Prostate cancer in the beginning with anti-androgen therapy has a good effect, after a period of treatment, the eventual development of androgen-independent prostate cancer, because there is no medicine for healing and death. Therefore, to prevent or delay prostate cancer from hormone-dependent to non-dependent transformation in the treatment of prostate cancer is very important. In this study, in order to delay after androgen deprivation therapy for prostate cancer to androgen-dependent shift as the starting point, through animal experiments to observe the kidney Stasis composition of the \mechanism. Firstly, cultured human androgen dependent cell line LNCaP cells, and the cells in nude mice were inoculated subcutaneously with Matrigel 1:1 mixture of prostate cancer animal model was prepared. After a successful modeling, places prostate cancer tumors in nude mice bearing as the research object, elimination of interference factors before cancer. When tumors in nude mice grew to 450mm3 so, were randomly divided into model group, pure traditional Chinese medicine group, castration alone group, castration Medicines four groups. Castration alone group, castration Medicines were given saline after removal of testicular cancer and the consumption of water decoction former model group, while pure traditional Chinese medicine group were given normal saline and pre-cancer elimination of water decoction, each 2 times a week measuring tumor volume, serum PSA1 times to dynamic changes in tumor volume was observed in nude mice, serum PSA changes; drug intervention animals were sacrificed after four weeks, the removal of tumor tissue weighing, paraffin-embedded sections, HE staining of tumor pathological immunohistochemical staining of tumor tissue PCNA, AR expression, TUNEL method apoptosis in tumor tissue was observed, Western Blot assay tumor tissue AKT-PI3K-PTEN phosphorylation and total protein expression and their ratio. Results 1 prostate cancer LNCaP cell culture and animal models prepared LNCaP cells cultured routinely collect appropriate index of proliferating cells and Matrigel 1:1 mixture, implanted subcutaneously in nude mice left armpit 3rd Week # 11 tumor gradually formation, assembly tumors was 100%, the peak of tumor at 4 weeks (23.2%) and 5 weeks (35.7%). Serum PSA concentration and tumor volume were highly correlated (R = 0.6403). 2 pre-cancer prostate cancer in nude mice to eliminate androgen-dependent transformation of the model group tumor volume continued to grow, up to end of the experiment (1189.22 ± 546.15) mm3; pure traditional Chinese medicine tumor volume continued to grow and grow faster in the beginning tumor volume greater than the model group, but later began to grow slows, end of the experiment was (1152.57 ± 892.62) mm3, no difference compared with the model group. Castration castration alone group continues to decrease after 0.5 weeks in 1-4 weeks, tumor volume was significantly smaller than the model group (P lt; 0.05), and reached the lowest in three weeks (286.57 ± 115.87) mm3; 3 weeks after tumor volume began to increase and continued to grow, up to end of the experiment (547.71 ± 235.42) mm3. Castration castration Medicines in tumor volume continued to decline, in one week, 1.5 weeks and two weeks the tumor volume was significantly smaller than castration alone group (P lt; 0.05); 2 weeks after no significant changes in tumor volume until the end of the experiment no re-growth of the tumor volume, end of the experiment was (265.00 ± 186.02) mm3, compared with castration alone group had significant difference (P lt; 0.05). The serum PSA and tumor volume trends consistent with trends, changes in serum levels of PSA expression changes in tumor volume than a week or so earlier. 3 pre-cancer tumor elimination of tumor tissue cell proliferation, apoptosis and the expression of the AR model group, HE staining showed strong tumor growth, a large capillary network, cells arranged in dense, visible pathological mitosis; tumor cells can be seen a large number of PCNA expression, TUNEL staining of apoptotic cells less. Medicines alone exuberant tumor growth, cancer nests surrounded by more mononuclear cell infiltration, PCNA expression in tumor cells less than the model group, apoptotic cells compared with the model group increased. Castration alone, compared with the model group, tumor stroma more, some cancer cells showed active form; higher rate of PCNA expression in some areas, but less compared with model group expression of apoptotic cells was significantly increased compared with the model group . Medicines castration compared with castration alone, tumor stroma more and more visible necrotic tumor cells and nuclear condensation, nuclear fragmentation cells; PCNA expression rate and less than the amount of apoptotic cells increased significantly. Model group, a large number of AR expression in tumor cells, pure traditional Chinese medicine group than in the untreated group were reduced; expression of AR castration alone group than in model group was significantly reduced, castration Medicines tumor cells expressing only a very small amount of AR, significantly less than castration alone . 4 Front eliminate cancer animal models of prostate cancer tumor tissue PI3K-AKT-PTEN signal transduction pathway in the relative value of phosphorylation of PI3K was no difference between the four groups; AKT phosphorylation level, pure traditional Chinese medicine group than in the model group decreased , castration alone group was significantly lower than the model group, castration and traditional Chinese medicine group was significantly lower than castration group; phosphorylation of PTEN expression, pure traditional Chinese medicine group than in the model group increased, castration alone group was significantly higher than the model group, go to potential plus TCM group was significantly higher than castration group. Conclusion 1 The model of tumor peak in the third and fourth weeks, occurred at about 3 weeks after castration hormone-dependent transformation. (2) pre-cancer can enhance the elimination of castration on the treatment of prostate cancer, and prostate cancer after castration to delay androgen-dependent transformation. But without the castration of androgen-dependent prostate cancer in the early certain role in promoting. Tips to kidney Stasis composed of herbal compound on the timing of treatment of prostate cancer. 3 pre-cancer elimination of tumor cells can be reduced AR expression, which may be related to treatment mechanism. 4 may be pre-cancer by promoting the elimination of PTEN phosphorylation and inhibition of AKT activation, thereby inhibiting tumor cell proliferation and apoptosis of tumor cells, delaying prostate cancer to androgen-dependent transformation.

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