Forkhead Box R2 Knockdown Decreases Chemoresistance to Cisplatin via MYC Pathway in Bladder Cancer
Forkhead Box R2 Knockdown Decreases Chemoresistance to Cisplatin via MYC Pathway in Bladder Cancer
复制标题
Forkhead Box R2 敲低通过 MYC 途径降低膀胱癌对顺铂的化疗耐药性
DOI：
10.12659/msm.917345
复制
发表时间：
2019-11-25
影响因子：
3.1
通讯作者：
He, Wei
中科院分区：
文献类型：
--
作者：
Li, Yangle;Zu, Xiongbing;He, Wei
膀胱癌是全球范围内非常常见的泌尿系统肿瘤，晚期膀胱癌患者需要以顺铂或吉西他滨为基础的化疗。许多膀胱癌患者对化疗反应较差，导致临床治疗失败。我们挖掘了GSE77883 GEO数据集，发现FoxR2在T24耐药细胞中是一个显著上调的基因。在此，我们评估了FoxR2在膀胱癌细胞化疗耐药中的作用。材料/方法通过增加顺铂浓度构建顺铂耐药T24 （T24/DDP）细胞，检测FoxR2在T24/DDP和T24细胞中的表达差异。分别在T24/DDP和T24细胞中建立FoxR2功能缺失和功能获得细胞模型。评估细胞存活、克隆形成、细胞周期和细胞凋亡，并验证MYC通路。结果FoxR2在T24/DDP细胞中表达明显上调。FoxR2在T24/DDP细胞中表达下调，降低了细胞存活率和克隆形成，抑制了G1/S期转变，促进了细胞凋亡。这些结果被T24细胞中FoxR2水平的恢复所逆转。我们发现FoxR2敲低可增强T24/DDP细胞对顺铂的敏感性，而MYC过表达可拮抗T24/DDP细胞的化学敏感性。结论FoxR2敲低可通过MYC途径降低膀胱癌细胞对顺铂的化疗耐药，这可能是克服膀胱癌化疗耐药的靶点。
Background Bladder cancer is a very common urological cancer globally, and cisplatin- or gemcitabine-based chemotherapy is essential for advanced bladder cancer patients. Many patients with bladder cancer have a relatively poor response to chemotherapy, leading to failure of clinical treatment. We mined the GSE77883 GEO dataset, identifying FoxR2 as being a significantly upregulated gene in T24 chemoresistant cells. Herein, we assessed how FoxR2 functions in bladder cancer cell chemoresistance. Material/Methods Cisplatin-resistant T24 (T24/DDP) cells were constructed by administering increasing concentrations of cisplatin, and differences in expression of FoxR2 were examined in T24/DDP and T24 cells. FoxR2 loss- and gain-of-function cells models were established in T24/DDP and T24 cells, respectively. Cell survival, clone formation, cell cycle, and cell apoptosis were assessed, and the MYC pathway was verified. Results FoxR2 was significantly upregulated in T24/DDP cells compared to T24 cells. Knockdown of FoxR2 in T24/DDP cells, survival rate, and clone formation were decreased, G1/S phase transition was suppressed, and cell apoptosis was promoted. These results were reversed by restoration of FoxR2 levels in T24 cells. We found that FoxR2 knockdown enhanced sensitivity to cisplatin, whereas MYC overexpression antagonized chemosensitivity in T24/DDP cells. Conclusions FoxR2 knockdown decreases chemoresistance to cisplatin via the MYC pathway in bladder cancer cells, and this may be a target for overcoming chemoresistance in bladder cancer.