Co‑culture of hepatocellular carcinoma cells and human umbilical endothelial cells damaged by SU11274
- Authors:
- Minoru Tomizawa
- Fuminobu Shinozaki
- Yasufumi Motoyoshi
- Takao Sugiyama
- Shigenori Yamamoto
- Naoki Ishige
View Affiliations
Affiliations: Department of Gastroenterology, National Hospital Organization Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan, Department of Radiology, National Hospital Organization Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan, Department of Neurology, National Hospital Organization Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan, Department of Rheumatology, National Hospital Organization Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan, Department of Pediatrics, National Hospital Organization Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan, Department of Neurosurgery, National Hospital Organization Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan
- Published online on: September 10, 2014 https://doi.org/10.3892/br.2014.361
-
Pages:
799-803
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Abstract
Mesenchymal‑epithelial transition factor (c‑Met) is a receptor that binds to the hepatocyte growth factor and is upregulated in hepatocellular carcinoma (HCC). The anti‑tumor effects of (3Z)‑N‑(3‑chlorophenyl)‑3‑({3,5‑dimethyl‑4‑[(4‑methyl-piperazin‑1‑yl)carbonyl]‑1H‑pyrrol‑2‑yl}methylene)‑N‑me-thyl‑2‑oxo‑2,3‑dihydro‑1H‑indole‑5‑sulfonamide (SU11274), a c‑Met inhibitor, were investigated in the present study. HCC cells (HLE, HLF, PLC/PRL/5, Hep3B, Huh‑6 and HepG2) and human umbilical vein endothelial cells (HUVECs) were used. Quantitative polymerase chain reaction was performed to detect the expression level of c‑Met in HCC and HUVECs, and cyclin D1 in HCC. The 3‑(4,5‑dimethylthiazol‑2‑yl)‑5‑(3‑car-boxymethoxyphenyl)‑2‑(4‑sulfophenyl)‑2H‑tetrazolium inner salt assay was performed to assess the proliferation of the HCC cells and HUVECs cultured with SU11274. Co‑culture of HLF or PLC/PRL/5 cells and HUVECs was established as an in vitro model of HCC tissues. The expression levels of c‑Met in HLE, HLF, PLC/PRL/5, Hep3B, Huh‑6 and HepG2, adult healthy liver and HUVECs were 4.43±0.50, 1.61±0.18, 3.70±0.08, 0.81±0.18, 6.60±1.29, 1.06±0.35, 1.00±0.09 and 88.8±17.3 (mean ± standard deviation), respectively. SU11274 (30 µM) suppressed the proliferation of HLF, PLC/PRL/5 and HUVECs to 11.0±9.4, 46.5±30.7 and 29.4±5.0%, respectively. SU11274 (30 µM) decreased the expression levels of cyclin D1 in HLF and PLC/PRL/5 cells to 45.1±11.6 and 30.1±10.3%, respectively. SU11274, at a concentration of 30 µM damaged the morphology of the co‑cultures of HLF or PLC/PRL/5 cells with HUVECs and all the cells died. c‑Met is highly expressed in HUVECs and HCC cells, but not in Hep3B. At a 30‑µM concentration, SU11274 suppresses the proliferation of HLF, PLC/PRL/5 and HUVECs. SU11274 (30 µM) damages the co‑cultures of HLF or PLC/PRL/5 cells with HUVECs.
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