Study on mechanism of AZD8055 inhibiting migration and EMT progression of cholangiocarcinoma cell HuCCT1
10.3969/j.issn.1001-1978.2019.10.018
- Author:
Xue WANG
1
Author Information
1. Cancer Research Center, Yanbian University
- Publication Type:Journal Article
- Keywords:
Akt/mTOR signaling pathway;
AZD8055;
Cholangiocarcinoma;
DEK;
EMT;
Migration;
Proliferation
- From:
Chinese Pharmacological Bulletin
2019;35(10):1429-1436
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the molecular mechanisms of the dual inhibitor of mammalian rapamycin target protein (mTOR) AZD8055 in migration and EMT process inhibition of the human cholangiocarcinoma cell line HuCCTl. Methods The viability of HuCCTl cells treated with different concentrations of AZD8055 was measured by MTT assay, and the colony formation ability of HuCCTl was detected by colony formation assay. The effect of AZD8055 on the motility of HuCCTl cells was examined by wound healing assay and Tran-swell assay. The expression levels of the protein associated with Akt/mTOR pathway, epithelial-mesenchymal transition (EMT) process and DEK were detected by Western blot. The interaction relationship between AZD8055, DEK and Akt signaling pathway was analyzed by STITCH and GeneMania databases. Cholangiocarcinoma cells'proliferation, migration capacities and Akt/mTOR signaling pathway-related protein expression levels were detected after DEK gene silencing. Results Compared with control group, AZD8055 inhibited the proliferation and migration capacities of cholangiocarcinoma cells, and suppressed the expression levels of Akt/mTOR signaling pathway-related markers, down-regulated DEK expression and inhibited EMT process. DEK silence significantly inhibited cell proliferation, migration and significantly decreased the phosphorylation levels of Akt, S6, and 4EBP1. Conclusions AZD8055 treatment inhibits the migration and EMT progression of HuCCTl cells, and its mechanism is associated with DEK down-regulation and inhibition of Akt/mTOR signaling pathway.
