| Autor: |
Myers, Jeffrey N., Holsinger, F. Christopher, Bekele, B. Nebiyou, Li, Emily, Jasser, Samar A., Killion, Jerald J., Fidler, Isaiah J. |
| Předmět: |
|
| Zdroj: |
Archives of Otolaryngology - Head & Neck Surgery; Aug2002, Vol. 128 Issue 8, p875, 5p |
| Abstrakt: |
Background: Overexpression of epidermal growth factor receptor (EGF-R) is associated with increased malignant potential and correlates with poor clinical outcome in head and neck cancer. Therefore, inhibition of the EGF-R pathway provides an ideal target for molecular therapy. We examined in vitro and in vivo effects of PKI166, an orally administered EGF-R inhibitor, on 2 human squamous cell carcinoma of the oral cavity cell lines, Tu159 and MDA1986. Study Design: Basic science, laboratory investigation. Results: For Western blotting, Tu159 and MDA1986 cells were pretreated for 1 hour and then stimulated with EGF. The EGF-R–specific tyrosine kinase autophosphorylation was inhibited completely by PKI166 at all doses tested (1-10 µg/mL). By means of a tetrazolium-based viable cell assay, PKI166 was shown to arrest the growth of Tu159 and MDA1986 cells. The inhibitory concentration (50%), calculated from regression lines on the linear portion of the growth inhibition graphs, was 0.18µM (R = 0.98) for Tu159 cells and 0.23µM (R = 0.97) for MDA1986 cells. Nude mice were inoculated subcutaneously with 1 × 10[sup 6] Tu159 tumor cells and observed for 7 days. Next, daily doses of PKI166 (0, 10, or 50 mg/kg) were delivered by orogastric lavage for 28 days and the animals were observed for tumor growth. PKI166 significantly reduced tumor growth in mice treated for 1 month with oral PKI166 in a dose-dependent fashion. Conclusions: Targeted molecular therapy with EGF-R blockade arrests the growth of oral cancer in vitro and reduces its proliferation in an experimental xenograft animal model. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
