| Background and ObjectivesThe prostate itself’s organization acinar cells anomalies differentiation leads to prostate cancer. In early years,it is thought to be a kind of threat to the Europe male reproductive cancer, But in the early days of the study has found that prostate cancer of the crowd has obvious racial differences and geographical differences. Prostate cancer mortality in euramerican developed countries and regions is in the second place of various malignant tumors. Although Asia countries, such as China,prostate cancer rate is lower than western countries, but the statistics show that China’s prostate cancer quickly rising up in recent years,it has become one of the common malignant tumors which threat to Chinese men’s health.The etiology of prostate cancer is not clear at present.It is of great difficult to make early diagnosis and treat the late prostate cancer patient.it still rely on prostate specific antigen(PSA),ultrasound test,biopsy through the rectum,proctogenous finger palpation or doctor’s experience to make the judgment. we usually take surgical resection as the main treatment today and give the endocrine and radiation and chemotherapy in the same time,but the effect is not perfect. After several years of surgical excision of the prostate cancer,it is likely to be the androgen-independent prostate cancer which is the late period of the cancer and it is hard to deal with. The occurrence and development of cancer is controled by a significant number of factors. It is shown by the researchs that excessive activation and expression of STAT3signal pathway in one’s body is related to a large number of hunman cancers. The STAT3signaling pathways played an important role in prostate cancer’s proliferation and development,it accelerate the tumor’s growth and make the disease worsen soon.JAK2is an important upstream kinase in STAT3signal transduction system. It is likely to raise the STAT3monomer in the cytoplasm after the activation of JAK,and make STAT3molecular tyrosine phosphorylation.after they quickly activate STAT3signaling pathways,it produce corresponding biological effect soon, and lead the promote of tumor proliferation. We will have a better or a perfect therapeutic method to the prostate cancer,especially the advanced cancer,if we can restrain STAT3signaling pathways in the prostate cancer. AG490is a kind of effective inhibitors to the JAK2kinase and have been widely used in a variety of the treatment of malignant tumor,such as hepatocellular carcinoma,leucocythemia,multiple myeloma and so on. There are few reports about the anti-cancer mechanism and influence of AG490in prostate cancer especially in hormone refractory prostate cancers.The goal of our experiment is to culture androgen independent DU145prostate cancer cells,and observe the influence of the cancer cells with different concentration of AG490.Detect the cells to make sure whether there exist the expression of signaling pathways STAT3and explore anticancer mechanisms of AG490drugs in androgen independent prostate cancer.Materials and Methods1.Culture DU145cells in vitro, Newborn calf serum, AG490drugs, Dulbecco’s modified eagle medium with high glucose,MTT, Dimethylsulfoxide, etc.2. The experiment are divided into two groups,one is the control group,another group is deal with four kinds of AG490concentrationl(10、25、50、80μmol/L) which are added into the DU145cells.Observe the absorbency A value and cell proliferation inhibition rate with different time(24,48,72h)by the method of MTT way and use the Western blot test method to test the expression of relevant members of protein in STAT3signaling pathways.3. It is the SPSS17.0software which is used to analyse the data got from experiment with the inspection standards a=0.05.ResultsFirst of all to add four kinds of AG490concentration to process the prostate cancer DU145cells with different time.It is obviously that AG490can significantly inhibit proliferation of DU145prostate cancer cells and promote its apoptosis. it is enhanced with the increasing doses (F=786.17,p<0.05) and enhanced with the time factors (F=354.57, p<0.05). We can see the interaction between time and does. there is a time and dose dependent from the inhibition fonction of AG490to DU145cells (F=60.58,p<0.05)Use the western blot method to detect the related members of protein in STAT3signaling pathways after72hours of process with different AG490concentrations in DU145cells. It is clearly shown that the expression of protein p-JAK2、STAT3、 p-STAT3are for significantly less and the expression level of target genes Cyclin D1and BCL-xL protein are obviously reduced.ConclusionsSTAT3signal transduction pathways and related components p-JAK2、STAT3、 p-STAT3、Cyclin D1and bcl-xL are widely expressed in human androgen-independent prostate cancer cells. AG490is the JAK2kinase inhibitors which can efficiently restrain the proliferation of hormone independence prostate cancer and promote the tumor cell apoptosis. It played an important role in the proliferation and apoptosis of prostate cancer DU145cells by STAT3signaling pathways. AG490can effectively block STAT3signaling pathways, thus inhibiting the development of prostate cancer... |
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