| Ovarian cancer ranks the second most common tumors of the female genital organs, and additionally, both the mortality rate and5-year survival rate of ovarian cancer rank the first. Currently, typical treatments of ovarian cancer consist of surgical resection in combination with postoperative chemotherapy with carboplatin and paclitaxel. However, the vast majority of patients with advanced disease relapse within five years, often caused by metastasis and drug resistance of ovarian cancer cells.SOX2is a very important stem cell marker protein, regulates some important genes, which play a key role in embryonic development, lens development and neuronal differentiation. SOX2is closely related to the maintenance of stem cell characteristics. In recent years, the studies also found that, SOX2is highly expressed in a variety of tumors, such as lung cancer, pancreatic cancer, breast cancer, glioma, prostate cancer. In these cancers, SOX2can affect tumor proliferation, migration, drug resistance, and many other features. But there is so litter in ovarian carcinoma. The main purpose of this project is to investigate the role of SOX2in migration, invasion and drug resistance in ovarian cancer.The efficacy of drugs for chemotherapy for ovarian cancer is not obvious, because of toxicity, non-targeted, so the therapeutic effect on patients is not very good.In this regard, we carried out targeting treatment for ovarian cancer, the goal is:directed drug to the ovarian cancer cells by targeting to increase the concentration of the drug around the ovarian cancer cells and reduce the concentration of the drug in other organs and blood, which can reduce toxicity.In the first section, through cell transfection technology to overexpress SOX2, the migration ability of ovarian cancer cells was significantly enhanced. At the same time, invasion assay also showed that SOX2can influence cells invasion. Gelatin zymography assays confirmed that the activities of metalloproteinases MMP-2and MMP-9were regulated by SOX2. We further explored the molecular mechanism of SOX2effect on ovarian cancer metastasis. We picked some cell migration induced genes, which were quantified by PCR between two cell lines. When SOX2was overexpressing, FN1, S100P were up-regulated. Western blot analysis also confirmed the expression of FN1, and through, the reporter gene system, SOX2can directly regulate FN1. Finally, we also used siRNA interference technology to observe the effect of FN1on cell migration.In the second section, we found cisplatin resistance was decreased after SOX2knockout by shRNA. Meantime, cisplatin resistance was increased after SOX2overexpression. In addition, we also found that SOX2was elevated by cisplatin inducing. We found some important genes, which were regulated by SOX2through chip screening.In the third section, we found the target proteins for ovarian cancer, ABHD2and F11R, through the MPSS and quantitative proteomics technologies. The target proteins is not only targeting ovarian cancer, is also targeting the resistant cells in ovarian cancer, which can improve the drug concentration surrounding the resistant cells. On the purpose of the targeted therapy for ovarian cancer, we screened the peptides, which can targeting the target proteins, by phage display technology.This study not only improves our understanding of SOX2on migration, drug resistance in ovarian cancer, but also provides some potential target proteins for ovarian cancer therapy. |
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