| ObjectiveIn recent years, the incidence of prostate cancer in China has grown rapidly, has been being the third in the reproductive system of male urinary malignancies. In the beginning, therapy of anti-androgen has a good effect. After a period of time, the development of androgen independent prostate cancer, and ultimately people die due to non-medicine treatment. So how to prevent or delay the transformation of prostate cancer from hormone dependence to non-dependent in prostate cancer is very important.Prostate Cancer Prescription was written by Wang Pei who works in East Hospital of Beijing University of Chinese Medicine. The transformation of prostate cancer from hormone dependence to non-dependent can be observed after castration in this study through animal experiments, and its possible molecular mechanism can be explored too.MethodsFirst, human cell line LNCaP was cultured, which is androgen dependent cells. Then cells with the 1:1 mixture 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 Prostate Cancer Prescription is intervening factors. When the tumor in nude mice grew to about 450mm3, randomly divided into model group, simple Chinese medicine group, simple ovariectomized group, ovariectomized plus Chinese medicine group, altogether 4 groups. Simple ovariectomized group and model were given saline and Prostate Cancer Prescription after the removal of testicular; ovariectomized plus Chinese medicine group and pure traditional Chinese medicine group were given saline and Prostate Cancer Prescription. Tumor volume was measured 2 times a week and serum PSA was measured 1 time a week, which is a dynamic observation of tumor volume in nude mice. Animals were sacrificed four weeks after drug intervention, removal of tumor, weight, HE staining of tumor histology, immunohistochemistry staining tumor for PCNA and AR expression, TLNEL for Apoptosis, Western Blot for the ratio of AKT-PI3K-PTEN phosphorylated protein and total protein Expression in tumor tissue.Results1 LNCaP cells culture and animal model LNCaP cells were cultured routinely, and were collected, with a 1:1 mixture of Matrigel, then implanted left armpit of nude mice subcutaneously.3 weeks later, assembly of tumor was 100%. Tumor generating peak at 4th week (23.2%) and 5th week (35.7%). Serum PSA concentration and tumor volume was highly correlated (R=0.6403).2 Prostate Cancer Prescription delay the transformation of the prostate cancer to androgen-dependent in nude mice In model group, the tumor volume continued to grow, end of the experiment of (1189.22±546.15) mm3; In simple Chinese medicine group, tumor volume continued to grow and grow faster in the beginning, tumor volume greater than the untreated group, but later slowed the growth, at the end of experiment reached (1152.57±892.62) mm3, no difference compared with model group. In simple ovariectomized group, tumor volume continued to decrease after 0.5 weeks, and in 1st -4th week, tumor volume was significantly smaller than the model group (P<0.05), and reached the lowest at 3 weeks (286.57±115.87) mm3; the tumor volume began to increase after 3 weeks, and continued to grow, at the end of the experiment up to (547.71±235.42) mm3. In ovariectomized plus Chinese medicine group, tumor volume continued to decline after castration, and at 1st week, 1.5th week and 2nd week, tumor volume was significantly smaller than the simple castration group (P<0.05); the tumor volume did not change significantly until the end of the experiment. The trends of the serum PSA was consistent with the trends of tumor volume, the changes in serum PSA was a week or so earlier than the changes in tumor volume.3. Influence of Prostate Cancer Prescription on tumor cell proliferation, apoptosis and expression of AR in tumor tissue. HE staining shows tumor flourishing, a large number of capillary network proliferation, tumor cells intensive arrangment with pathological mitotic phase, a large number of PCNA expression in tumor cells and TUNEL-positive apoptotic cells is less in model group. HE staining of simple Chinese medicine group shows tumor flourishing with a large number of mononuclear cell infiltration around the cancer nests, PCNA expression in tumor cells less than the model group, the apoptotic cells increased compared with model group. Compared with model group, in simple ovariectomized group, tumor stroma is more and a part of cancer cells are active, PCNA expression is higher in some areas but less than model group and apoptotic cells significantly increase. Compared with Simple ovariectomized group, in ovariectomized plus Chinese medicine group, tumor stroma is more, more necrotic tumor cells and nuclear condensation and nuclear fragmentation of cells can be obserced, PCNA expression is less and the amount of apoptotic cells increase significantly. Regarding expression of AR, it shows that high expression in tumor cells of model group, AR in simple Chinese medicine group is less than model group; AR expression in Simple ovariectomized group was significantly less than the model groups, there is only a very small amount of tumor cells expressing AR in ovariectomized plus Chinese medicine group, significantly less than Simple ovariectomized group.4 Prostate Cancer Prescription changes PI3K-AKT-PTEN signal transduction pathway in the prostate cancer tumor tissue of the animal model the relative value of PI3K phosphorylation is no difference between the four groups; The level of AKT phosphorylation in model group was more than that in simple Chinese medicine group, the model group was significantly more than simple ovariectomized group; the expression of PTEN phosphorylation, simple Chinese medicine group is more than in model group, the model group was significantly higher than simple ovariectomized group, simple ovariectomized group and simple Chinese medicine group was significantly higher than the ovariectomized group. Conclusion1. The model tumor peak at 3rd and 4th week; hormone-dependent transf ormation occurred at about 3 weeks after castration.2. The treatment of prostate cancer was enhanced by Prostate Cancer P rescription and androgen-dependent transformation were delay after ca stration. But without castration in androgen independent prostate can cer have a certain role in promoting early.3. The expression of AR can be reduced by Prostate Cancer Prescriptio n, which may be related to its therapeutic mechanism.4. Prostate Cancer Prescription may inhibit tumor cell proliferation by promoting PTEN activation and inactivation of AKT, thereby promote apoptosis of tumor cells, anti the transformation of Androgen independent prostate cancer. |
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