TY - JOUR
T1 - Targeted molecular therapy for oral cancer with epidermal growth factor receptor blockade
T2 - A preliminary report
AU - Myers, Jeffrey N.
AU - Holsinger, Christopher
AU - Nebiyou Bekele, B.
AU - Li, Emily
AU - Jasser, Samar A.
AU - Killion, Jerald J.
AU - Fidler, Isaiah J.
PY - 2002
Y1 - 2002
N2 - 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 Tu 159 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 × 106 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.
AB - 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 Tu 159 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 × 106 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.
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U2 - 10.1001/archotol.128.8.875
DO - 10.1001/archotol.128.8.875
M3 - Article
C2 - 12162763
AN - SCOPUS:0036340532
SN - 0886-4470
VL - 128
SP - 875
EP - 879
JO - Archives of Otolaryngology - Head and Neck Surgery
JF - Archives of Otolaryngology - Head and Neck Surgery
IS - 8
ER -