The Role Of FoxM1 In The Process Of Epithelial-mesenchymal Transition In Prostate Cancer

Object Prostate cancer (PCa) is one of the malignant tumors which is a threat to the health of older men worldwide. The incidence of prostate cancer in China has been increasing significantly. Prostate cancer treatment options usually depends on whether there is invasion and metastasis in surrounding tissue. Therefore study of early diagnosis and metastasis mechanism is important. FoxMl involve in multiple aspects of tumorigenesis, and epithelial-mesenchymal transition (EMT) is an key process during metastasis. Shear wave elastography (SWE) is an important method for identification of benign and malignant tumor. Based on the above background, this study aimed at detecting expression of FoxM1 in prostate cancer tissues; studying the mechanisms of FoxMl involved in EMT and regulation factors in prostate cancer; preliminary studying shear wave elastography evaluating the elasticity of human prostate cancer xenografts tumors and its histopathological basis. Methods 1. Identification of FoxMl expression in prostate cancer. The protein and subtype expression was detected in prostate cancer tissues, benign prostate hyperplasia tissues and prostate cancer cells. The correlation between FoxM1 expression and Gleason grading was analyzed.2. FoxM1 involved in EMT in prostate cancer in vitro. The model of prostate cancer cell EMT was establishing. Changes of expression of FoxMl and EMT relative protein were observe and the mobility and migration ability of cells were evaluated. Metformin and hypoxia treated prostate cancer cells respectively, above parameters were detected.3. FoxMl involved in EMT in prostate cancer in vivo. A recombinant lentiviral vector that co-expressing GFP and FoxM1 shRNA was constructed. The stably expressing GFP and FoxMl shRNA prostate cancer cell line and nude mouse xenograft model were established. The growth, proliferation and metastasis of xenograft tumors were recorded.4. The stiffness of PCa xenograft tumors was evaluated by SWE. Human PCa xenograft implantation model was established. The size of tumors in different growth time (6w,8w,10w) were detected by gray scale ultrasound. The stiffness of tumors were investigated using SWE. Compared the pathological features of tumors of varying elasticity. FoxMl knockdown PCa xenograft tumors were established. Detected parameters above at 8w.Results 1. There was difference expression of FoxM1 between PCa and BPH tissues. FoxMl expression levels were higher in the tissues with a Gleason score ≥7 compared with those with a Gleason score<7. Expression of FoxM1c were higher in PCa tissues and cells.2. TGF-P induced EMT in PCa cells. The expression of E-cadherin decreased, while vimentin and Slug increased. And the mobility and migration increased. The knockdown of FoxM1 reversed EMT. After treatment of metformin, expression of FoxM1 decreased and migration ability of PCa cells decreased.While in hypoxia condition, expression of FoxM1 increased significantly and that promoted EMT and migration ability of PCa cells.3. FoxM1 shRNA lentivirus vectors with GFP were successfully constructed and FoxM1 knockdown PCa xenograft model was established. The growth, proliferation and metastasis abilities were lower in FoxM1 knockdown PCa xenograft tumors than that in the control group tumors.4. The volume were 832.58±142.98,1862.76±271.8 and 2764.2±255.93mm3 (p<0.05) in tumors of 6w,8w and lOw. The mean Young’s modulus were 22.11±2.45,44.89±3.02 and 57.41±3.98KPa (p<0.05)respectively. The collagen fibers increased in the stiff tumor tissues and collagen I type was the main type. And expression of a-SMA was higher. In FoxMl knockdown groups, the tumors grew slowly. The volumes were 813.7686±111.1932 and 1921.297±258.1513mm3 (p<0.05) in FoxM1 knockdown groups and control groups, and the mean Young’s modulus were 25.46±3.48 and 46.94±5.32KPa (p<0.05). The collagen fibers were fewer in FoxMl knockdown tumor tissues. And expression of a-SMA was weak.Conclusion The expression of FoxM1 increased in PCa tissue and is related with Gleason grading. FoxM1 has a significant role in the EMT process of PCa and it could be an novel target of PCa treatment. SWE can evaluate elasticity of PCa xenograft tumors and it is an important method in PCa diagnosis.