| Abstract | The development of paclitaxel-resistance in tumors is one of the most significant obstacles to successful therapy. Thymosin-beta-4 (TB4) has been known as actin-sequestering protein and functions in tumor metastasis. Here, we overexpressed TB4 in HeLa cells (TB4-HeLa) and examined the effect of TB4 in paclitaxel-induced cell death. TB4-HeLa cells showed a higher growth rate and a lower percentage of basal apoptosis than HeLa cells. TB4-HeLa cells were more resistant to paclitaxel-induced cell death than HeLa cells. TB4 transcript expression with paclitaxel treatment was dose-dependently increased in HeLa cells but that was not in TB4-HeLa cells. Small interfering RNA (siRNA) of TB4 inhibited HeLa cell growth and enhanced paclitaxel-induced cell death. Basal ERK phosphorylation was elevated and basal p38 kinase phosphorylation was reduced in paclitaxel non-treated TB4-HeLa cells. When treated with paclitaxel, cell death and resistance-induction were independent of ERK and p38 kinase activation. Paclitaxel-resistance of TB4-HeLa cells was overcome by the inhibition of basal ERK activity with PD98059 pre-treatment. The inhibition of basal p38 kinase activity with SB203580 pre-treatment attenuated the paclitaxel-induced HeLa cell death. In conclusion, TB4 induced paclitaxel-resistance through the elevation of basal level of ERK phosphorylation. Therefore, TB4 could be a novel target to regulate paclitaxel-resistance. |
| Authors | Su-Young Oh, Ji-Hee Song, Jung-Eun Gil, Jeong-Hee Kim, Young-Il Yeom, Eun-Yi Moon
(Affiliation: Department of Human Genomics, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Taejeon 305-806, Korea.)
|
| Journal | Experimental cell research
(Exp Cell Res)
Vol. 312
Issue 9
Pg. 1651-7
(May 15 2006)
ISSN: 0014-4827 United States |
| PMID | 16515784
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Antineoplastic Agents, Phytogenic
- Enzyme Inhibitors
- Flavonoids
- Imidazoles
- PD 98059
- Pyridines
- RNA, Small Interfering
- SB 203580
- Paclitaxel
- Thymosin
- thymosin beta(4)
- Extracellular Signal-Regulated MAP Kinases
- p38 Mitogen-Activated Protein Kinases
- ras Proteins
|
| Topics |
- Animals
- Antineoplastic Agents, Phytogenic
(pharmacology)
- Apoptosis
(drug effects, genetics)
- Cell Proliferation
- Cell Survival
(drug effects, genetics)
- Drug Resistance, Neoplasm
(genetics)
- Enzyme Activation
- Enzyme Inhibitors
(pharmacology)
- Extracellular Signal-Regulated MAP Kinases
(metabolism)
- Flavonoids
(pharmacology)
- Gene Expression Regulation, Neoplastic
- Hela Cells
- Humans
- Imidazoles
(pharmacology)
- Mice
- NIH 3T3 Cells
- Paclitaxel
(pharmacology)
- Phosphorylation
(drug effects)
- Pyridines
(pharmacology)
- RNA, Small Interfering
(genetics)
- Thymosin
(genetics, metabolism)
- Transfection
- p38 Mitogen-Activated Protein Kinases
(metabolism)
- ras Proteins
(genetics)
|
