miR-381, a novel intrinsic WEE1 inhibitor, sensitizes renal cancer cells to 5-FU by up-regulation of Cdc2 activities in 786-O

被引：51

作者：

Chen, Binghai ^{[1
,2
]}

Duan, Lujing ^{[3
]}

Yin, Guangming ^{[1
]}

Tan, Jing ^{[1
]}

Jiang, Xianzhen ^{[1
]}

机构：

[1] Cent S Univ, Xiang Ya Hosp 3, Dept Urol, Changsha 410000, Hunan, Peoples R China

[2] Jiangsu Univ, Affiliated Hosp, Dept Urol, Zhenjiang, Peoples R China

[3] Jiangsu Univ, Affiliated Hosp, Dept Endocrinol, Zhenjiang, Peoples R China

来源：

JOURNAL OF CHEMOTHERAPY | 2013年 / 25卷 / 04期

关键词：

5-FU; Cdc2; Chemotherapy; MicroRNA; miR-381; Renal cell cancer; WEE1; GENE-EXPRESSION; DOWN-REGULATION; KINASE; CHECKPOINT; CARCINOMA; MICRORNA; RADIOSENSITIZATION; IDENTIFICATION; PHOSPHATASES; PD0166285;

D O I：

10.1179/1973947813Y.0000000092

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Few researches on increase of chemotherapy sensitivity by microRNA (miRNA) were reported. We aim to investigate exact role of miR-381 in chemotherapy sensitivity of 5-fluorouracil (5-FU) in renal cancer cells. Methods: We investigated the cell survival, cell-cycle and apoptosis of 786-O and HK-2 cells treated with miR-381 and 5-FU. IC50 of 5-FU was calculated. To study apoptosis and G(2)/M arrest, we determined pHH3, mitotic index and caspase-3/7 activity. Results: We showed that miR-381 combined with 5-FU inhibited proliferation and potentiated the antitumour efficacies of 5-FU at tolerated concentration in vitro. miR-381 combined with 5-FU led to Cdc2 activation, mitotic catastrophe, and cell apoptosis through inhibitory WEE1. WEE1 was also validated as the direct target of miR-381. IC50 of 5-FU decreased significantly in the presence of miR-381. Conclusion: miR-381 increases sensitivity of 786-O cells to 5-FU by inhibitory WEE1 and increase of Cdc2 activity.

引用

页码：229 / 238

页数：10