膀胱癌中 UNC5D 的下调：UNC5D 作为顺铂诱导膀胱癌细胞凋亡的可能介质。
Down-regulation of UNC5D in bladder cancer: UNC5D as a possible mediator of cisplatin induced apoptosis in bladder cancer cells.
机构信息
Department of Urology, First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China; Institute of Urology, China Medical University, Shenyang, People's Republic of China.
Department of Reproductive Biology and Transgenic Animals, China Medical University, Shenyang, People's Republic of China.
出版信息
J Urol. 2014 Aug;192(2):575-82. doi: 10.1016/j.juro.2014.01.108. Epub 2014 Feb 8.
PURPOSE
Identifying potential targets would improve therapeutic planning and disease management. Therefore, we investigated whether the novel identified dependence receptor UNC5D acts as a tumor suppressor in bladder malignancies.
MATERIALS AND METHODS
We assessed the UNC5D level in a panel of 15 primary bladder carcinomas and 6 cell lines using real-time reverse transcriptase-polymerase chain reaction and Western blot. MTT assay, TUNEL staining, colony formation assay and Western blot were done in cells untransfected and transfected with UNC5D vector, siUNC5D or siDAPK.
RESULTS
UNC5D was dramatically down-regulated in bladder cancer tissue samples and malignant cell lines. Restoration of UNC5D expression in bladder cancer cells lacking endogenous UNC5D expression suppressed cell proliferation and survival. Cisplatin treatment significantly induced UNC5D expression and DAPK dephosphorylation while UNC5D knockdown decreased bladder cancer cell sensitivity to cisplatin. DAPK silencing significantly inhibited the effect of UNC5D on apoptosis induced by cisplatin.
CONCLUSIONS
Our study suggests that UNC5D may have important roles as a novel suppressor in bladder cancer via the UNC5D/DAPK pathway.
目的
确定潜在的靶点可以改善治疗计划和疾病管理。因此，我们研究了新发现的依赖受体 UNC5D 是否在膀胱癌恶性肿瘤中作为肿瘤抑制因子发挥作用。
材料和方法
我们使用实时逆转录聚合酶链反应和 Western blot 检测了 15 个原发性膀胱癌和 6 个细胞系中 UNC5D 的水平。未转染和转染 UNC5D 载体、siUNC5D 或 siDAPK 的细胞进行 MTT 测定、TUNEL 染色、集落形成测定和 Western blot。
结果
UNC5D 在膀胱癌组织样本和恶性细胞系中明显下调。在缺乏内源性 UNC5D 表达的膀胱癌细胞中恢复 UNC5D 表达抑制了细胞增殖和存活。顺铂处理显著诱导 UNC5D 表达和 DAPK 去磷酸化，而 UNC5D 敲低降低了膀胱癌细胞对顺铂的敏感性。DAPK 沉默显著抑制了 UNC5D 对顺铂诱导的细胞凋亡的影响。
结论
我们的研究表明，UNC5D 可能通过 UNC5D/DAPK 通路在膀胱癌中作为一种新的抑制因子发挥重要作用。
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