Introduction
Bladder transitional cell carcinoma (BTCC) is one of the most prevalent human malignant diseases. Gemcitabine is commonly applied in the treatment of BTCC while acquired gemcitabine resistance has caused a severe impediment to recovery. This study aimed to investigate the function of DRAM2 in regulating gemcitabine resistance of BTCC.

Material and methods
GSE77883 was introduced to screen out the differentially expressed autophagy-related genes in T24 cells and gemcitabine-resistant T24-GEM cells. After establishing T24-GEM cells ourselves, aberrant expression of DRAM2 was detected by qRT-PCR and Western blot. After stably manipulating the expression of DRAM2 in T24 and T24-GEM cells, the changes of cell biological functions under gemcitabine treatment were compared, including cell viability, apoptosis and autophagy, using colony formation, flow cytometry and electron microscopy respectively.

Results
DRAM2 was up-regulated in gemcitabine-resistant T24-GEM cells. Silencing of DRAM2 in T24-GEM cells inhibited the cell autophagy induced by treatment with gemcitabine and contributed to attenuated gemcitabine resistance. Also, overexpression of DRAM2 in T24 cells enhanced the autophagy, strengthened the chemoresistance and decreased the cell apoptosis rate under the treatment with gemcitabine.

Conclusions
Our data suggested that downregulation of DRAM2 rescued the sensitivity of T24-GEM cells to gemcitabine, providing an appropriate therapeutic target for BTCC treatment.



中文翻译：

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DRAM2的上调促进膀胱移行细胞癌对吉西他滨的耐受性。

简介
膀胱移行细胞癌 (BTCC) 是人类最常见的恶性疾病之一。吉西他滨通常用于治疗 BTCC，而获得性吉西他滨耐药性严重阻碍了康复。本研究旨在探讨DRAM2在调节BTCC吉西他滨耐药中的作用。

材料与方法
引入GSE77883筛选出T24细胞和吉西他滨耐药T24-GEM细胞中差异表达的自噬相关基因。在自己建立T24-GEM细胞后，通过qRT-PCR和Western blot检测到DRAM2的异常表达。在稳定调控DRAM2在T24和T24-GEM细胞中的表达后，分别采用集落形成、流式细胞仪和电镜比较吉西他滨处理下细胞生物学功能的变化，包括细胞活力、凋亡和自噬。

结果
DRAM2 在抗吉西他滨的 T24-GEM 细胞中上调。T24-GEM 细胞中 DRAM2 的沉默抑制了吉西他滨治疗诱导的细胞自噬，并有助于减弱吉西他滨耐药性。此外，在吉西他滨治疗下，T24 细胞中 DRAM2 的过表达增强了自噬，增强了化学抗性并降低了细胞凋亡率。

结论
我们的数据表明，DRAM2 的下调挽救了 T24-GEM 细胞对吉西他滨的敏感性，为 BTCC 治疗提供了合适的治疗靶点。