25-甲氧基-達瑪烷-3β、12β、20-三醇和青蒿素通過下調睪丸特異性蛋白酶50 (TSP50)表達協同抑制MDA-MB-231細胞增殖

2016年4月，東北師范大學可用藥基因與蛋白篩選國家工程實驗室；東北師范大學農業與醫藥基因工程教育部研究中心；沈陽藥科大學食品科學工程學院；東北師范大學遺傳與細胞學研究所(National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China；Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University,Changchun 130024, China；Food Science Engineering, Shenyang Pharmaceutical University,Shenyang 110016, China；Institute of Genetics and Cytology, Northeast Normal University,Changchun 130024, China) Danfeng Wang老師研究團隊在《Tumor Biology》上發表論文：

“25-methoxyl-dammarane-3β, 12β, 20-triol and artemisinin synergistically inhibit MDA-MB-231 cell proliferation through downregulation of testes-specific protease 50 (TSP50) expression”

“25-甲氧基-達瑪烷-3β、12β、20-三醇和青蒿素通過下調睪丸特異性蛋白酶50 (TSP50)表達協同抑制MDA-MB-231細胞增殖”

Abstract：

Purpose: To explore the biological functions and mechanism of Opa interacting protein 5 (OIP5) in bladder cancer (BC).

Methods: We investigated the expression of OIP5 in BC through immunohistochemical staining (IHC) and its correlation with clinicopathologic features of BC patients. Moreover, knockdown of OIP5 was performed in BC cell lines and colony formation capacity, cell growth curve, cell cycle phase and cell apoptosis assay was applied for investigating the roles of OIP5 in BC. Moreover, the expression of OIP5 was validated through the Cancer Genome Atlas (TCGA) database. The diagnosis value of OIP5 was accessed by receiver operating characteristic (ROC) analysis in TCGA database.

Results: The expression of OIP5 in BC tissues was significantly higher than that in adjacent non-tumor tissues and bladder mucosa tissues with chronic cystitis. Higher protein expression level of OIP5 predicted shorter survival time in patients with BC, which was significantly correlated with larger tumor size, high-grade tumor and advanced T classification. The expression of OIP5 was considerably decreased after lentivirus infection both at mRNA and protein levels. Functional assay displayed that silencing of OIP5 inhibited colony formation capacity and cell growth in BC cell lines. Cell cycle assays indicated that suppressed OIP5 disturbed the balance of the cell cycle in BC cell lines, which increased the cell population of the G1 phase and decreased the cell population of the S phase. Furthermore, knockdown of OIP5 expression enhanced cell apoptosis process. The expression of OIP5 was significantly up-regulated in BC compared with adjacent non-tumor tissues based on TCGA database. OIP5 had the potential diagnostic value for BC.

Conclusions: Our work demonstrated that OIP5 might function as an oncogene to promote colony formation capacity and cell growth, arrest cell cycle and suppress cell apoptosis in bladder cancer.

摘要：

目的:探討Opa相互作用蛋白5 (Opa interacting protein 5, OIP5)在膀胱癌(BC)中的生物學功能及機制。

方法:通過免疫組化染色(IHC)研究OIP5在BC中的表達及其與BC患者臨床病理特征的相關性。在BC細胞株上敲低OIP5，通過集落形成能力、細胞生長曲線、細胞周期和細胞凋亡等實驗研究OIP5在BC中的作用。此外，通過癌癥基因組圖譜(TCGA)數據庫驗證OIP5的表達。通過TCGA數據庫的受試者工作特征(ROC)分析獲得OIP5的診斷價值。

結果:慢性膀胱炎患者BC組織中OIP5的表達明顯高于癌旁非腫瘤組織和膀胱黏膜組織。OIP5蛋白表達水平越高，BC患者生存時間越短，且與腫瘤大小較大、腫瘤級別高、T分期高相關。慢病毒感染后，OIP5在mRNA和蛋白水平上的表達均顯著降低。功能實驗表明，OIP5的沉默抑制了BC細胞系的集落形成能力和細胞生長。細胞周期實驗表明，抑制OIP5擾亂了BC細胞系細胞周期的平衡，使G1期細胞數量增加，S期細胞數量減少。此外，OIP5表達下調可促進細胞凋亡過程。TCGA數據庫顯示，與癌旁非腫瘤組織相比，BC組織中OIP5的表達明顯上調。OIP5對BC有潛在的診斷價值。

結論:OIP5可能作為癌基因在膀胱癌中具有促進細胞集落形成能力和細胞生長、阻滯細胞周期和抑制細胞凋亡的作用。

該論文中，人膀胱癌T24細胞(BC-T24)、人胚胎腎(HEK) 293T細胞和人膀胱癌5637細胞(BC-5637)的體外培養是使用Ausbian特級胎牛血清完成的。欲了解或購買Ausbian特級胎牛血清可以聯系北京締一生物400-166-8600.