SerpinB3蛋白表达上调促进前列腺癌进展的研究

Overexpression of SerpinB3 in prostate cancer promotes tumor cell progression

摘要:

目的：探讨丝氨酸蛋白酶抑制剂因子B3基因（serine protease inhibitor，SerpinB3）与前列腺癌的相关性。方法：运用Western blot方法检测SerpinB3蛋白在29例前列腺癌组织和35例正常对照前列腺增生组织中的表达差异；免疫组织化学方法检测SerpinB3蛋白在48例各期前列腺癌组织，33例良性对照组织芯片中的表达差异。应用脂质体法将合成的SerpinB3小干扰RNA（small interfering RNA，siRNA）瞬转前列腺癌DU145及PC3细胞；分为SerpinB3-siRNA1、SerpinB3-siRNA2和SerpinB3-siRNA3，随机干扰SerpinB3-siRNA-NC为阴性对照，未转染为空白对照组。选择干扰最佳的实验组行后续细胞迁移实验；判断干扰SerpinB3基因表达后对前列腺癌DU145及PC3细胞侵袭能力的影响。结果：Western blot证实SerpinB3蛋白在前列腺癌组织中的表达均高于对应的良性组织（P<0.001）；免疫组化检测发现SerpinB3蛋白在前列腺癌和良性组织中染色强度差异明显（P<0.001）；SerpinB3蛋白表达情况和患者年龄、肿瘤是否转移间无统计学差异（P=0.268，P=0.178）；和肿瘤病理及临床分期组间差异明显（P=0.031，P=0.042）。SerpinB3-siRNA能明显抑制肿瘤细胞迁移。结论：SerpinB3蛋白的明显上调表达能增强前列腺癌细胞侵袭能力。

Abstract:

Objective：To study the relativity between serine protease inhibitor（SerpinB3） and prostate cancer. Methods：Western blot was used to determine the SerpinB3 levels in 29 cases of prostate cancer tissues and 35 cases of prostate hyperplasia tissues，and im－munohistochemistry was used to detect the expression of SerpinB3 in 48 cases of prostate cancer tissues and 33 cases of prostate hy－perplasia tissues. The SerpinB3 small interfering RNA（siRNA） was transiently transfected into DU145 and PC3 cells by liposome method，including SerpinB3-siRNA1，SerpinB3-siRNA2 and SerpinB3-siRNA3. Random disturbance SerpinB3-siRNA-NC was used as negative control，and cells without transfection were blank control. SerpinB3-siRNA with the highest efficiency was chosen for sub－sequent cell migration assay in order to detect the effects of SerpinB3 on the invasion ability of DUl45 and PC3 cells. Results：Western blot results showed that the level of SerpinB3 protein in the tissues of prostate cancer was higher than that of the benign group（P<0.001）. Immunohistochemistry results showed SerpinB3 protein level was significantly higher in tumor tissues than that in benign tis－sues（P<0.001）. There was no statistic difference between SerpinB3 expression and the patient’s age and tumor metastasis（P=0.268，P=0.178，respectively），but SerpinB3 expression was significantly correlated with pathological grade and clinical stage of the tumor（P=0.031，P=0.042，respectively）. SerpinB3-siRNA could inhibit the proliferation and invasion of the cancer cells. Conclusion：Over expression of SerpinB3 can increase the invasion ability of prostate cancer cells.