| Experiment ID | EXP00350 |
| Reference | Title: Mechanism of gemcitabine-induced suppression of human cholangiocellular carcinomacell growth. Author: Toyota Y, Iwama H, Kato K, Tani J, Katsura A, Miyata M,Fujiwara S, Fujita K, Sakamoto T, Fujimori T, Okura R, KobayashiK, Tadokoro T, Mimura S, Nomura T, Miyoshi H, Morishita A,Kamada H, Yoneyama H, Okano K, Suzuki Y, Masaki T. Journal: Int J Oncol. 2015 Oct;47(4):1293-302. doi: 10.3892/ijo.2015.3118. Epub 2015 Aug7. Abstract: Although gemcitabine (2',2'-difluorocytidine monohydrochloride) is a commonanticancer agent of cholangiocellular carcinoma (CCC), its growth inhibitoryeffects and gemcitabine resistance in CCC cells are poorly understood. Our aimswere to uncover the mechanism underlying the antitumor effect of gemcitabine and to analyze the mechanism regulating in vitro CCC cell gemcitabine resistance. In addition, we sought to identify miRNAs associated with the antitumor effects ofgemcitabine in CCCs. Using a cell proliferation assay and flow cytometry, weexamined the ability of gemcitabine to inhibit cell proliferation in three types of human CCC cell lines (HuCCT-1, Huh28, TKKK). We also employed western blottingto investigate the effects of gemcitabine on cell cycle-related molecules in CCC cells. In addition, we used array chips to assess gemcitabine-mediated changes inangiogenic molecules and activated tyrosine kinase receptors in CCC cells. Weused miRNA array chips to comprehensively analyze gemcitabine-induced miRNAs and examined clusters of differentially expressed miRNAs in cells with and withoutgemcitabine treatment. Gemcitabine inhibited cell proliferation in a dose- andtime-dependent manner in HuCCT-1 cells, whereas cell proliferation was unchanged in Huh28 and TKKK cells. Gemcitabine inhibited cell cycle progression in HuCCT-1 cells from G0/G1 to S phase, resulting in G1 cell cycle arrest due to thereduction of cyclin D1 expression. In addition, gemcitabine upregulated theangiogenic molecules IL-6, IL-8, ENA-78 and MCP-1. In TKKK cells, by contrast,gemcitabine did not arrest the cell cycle or modify angiogenic molecules.Furthermore, in gemcitabine-sensitive HuCCT-1 cells, gemcitabine markedly alteredmiRNA expression. The miRNAs and angiogenic molecules altered by gemcitabinecontribute to the inhibition of tumor growth in vitro. PMID: 26252371 |
| Expressiion Profile | Description: Study of microRNA associated with the anti-tumor effect of gemcitabine Organism: Homo sapiens GEO ID: GSE67257 Platform: GPL18941 Number of samples: 20 |
| Design and Sample | Cancer Type: biliary tract cancer Cancer SubType: cholangiocellular carcinoma Cell Line: CCC cells Experimental Design: treatment Case Sample: cholangiocellular carcinoma treated with gemcitabine Control Sample: cholangiocellular carcinoma Num of Case: 10 Num of Control: 10 Quantification Software: limma Num of miRNAs: 2555 |
| Identification | Num of Up: 1 Num of Down: 0 |