Rosiglitazone enhances 5-fluorouracil-induced cell growth inhibition in hepatocellular carcinoma cell line Hep3B
| Autor: | Liang-qi Cao, Jian-bin Xiao, Zi-li Shao, Ting Xia, He-ping Peng |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
Antimetabolites Antineoplastic Carcinoma Hepatocellular Mice Nude Pharmacology Rosiglitazone Mice In vivo Cell Line Tumor Animals Humans PTEN Medicine MTT assay Gene Silencing Viability assay RNA Small Interfering Receptor Cell Proliferation Mice Inbred BALB C biology Traditional medicine Cell growth business.industry Liver Neoplasms PTEN Phosphohydrolase Drug Synergism Tumor Burden PPAR gamma Oncology Cell culture biology.protein Female Thiazolidinediones Fluorouracil business Neoplasm Transplantation Signal Transduction medicine.drug |
| Zdroj: | Chinese Journal of Cancer. 29:741-746 |
| ISSN: | 1944-446X 1000-467X |
| Popis: | BACKGROUND AND OBJECTIVE Rosiglitazone is a peroxisome proliferators-activated receptor gamma (PPARgamma) ligand, which inhibits tumor growth by activating PPARgamma signaling pathways. Fluorouracil (5-FU) is one of the commonly used chemotherapeutic drugs. However, patients develop drug resistance of 5-FU over time. The aim of this study was to investigate whether rosiglitazone can enhance 5-FU-induced cell growth inhibition and to explore its potential mechanisms. METHODS Cell viability was measured using MTT assay. Protein expression levels were detected by Western blot analysis. Small interference RNA was utilized to knockout PPARgamma and PTEN in Hep3B cells. RESULTS After 48 h of treatment with 10, 20, and 40 µmol/L rosiglitazone, the viability of Hep3B cells was (78.0 ± 2.7)%, (37.3 ± 8.1)%, and (19.8 ± 2.2)%, respectively (compared with control group, P values were all < 0.001). After 48 h of treatment with 10 µmol/L 5-FU, the viability of Hep3B cells was about (82.6 ± 3.9)%. When cells were treated with 10 µmol/L 5-FU in combination with either 10, 20 or 40 µmol/L rosiglitazone, the cell viability was (51.6 ± 5.4)%, (14.8 ± 4.2)%, and (8.5 ± 0.9)%, with corresponding q value of 1.36, 1.23, and 1.19, respectively. These data suggested that the two drugs had synergic effect in inhibiting Hep3B cell growth, which was further confirmed in an in vivo mice model. Subsequent investigations showed that rosiglitazone activated PPARgamma signaling pathways and increased the expression of PTEN. CONCLUSIONS Rosiglitazone enhances 5-FU-induced cell growth inhibition of Hep3B cells. |
| Databáze: | OpenAIRE |
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