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Antibodies to prion protein inhibit human colon cancer cell growth
Tumor Biology, 06/16/09
McEwan JF et al. - In a trial to test whether antibodies to prion protein (PrP) could induce apoptosis and be utilised in the treatment of cancers, data suggest a potential pharmacological application for PrP antibodies in combination chemotherapy.
Methods- Various antibodies to PrP were screened in MTT proliferation assays with HCT 116 colon cancer cells.
- Antibodies were shown to have varying degrees of anti-proliferative activity, with 3F4 and 6D11 essentially inactive, vs other highly active antibodies.
- BAR221 and F89/160.1.5 antibodies were particularly potent and afforded >40% reduction in proliferation at 50 μg/ml.
- In combination therapy experiments, antibodies to PrP enhanced the effect of irinotecan, 5-FU, cisplatin, and doxorubicin to varying degrees.
- Use of PrP antibody in vitro resulted in increased apoptosis as measured by reduced Bcl-2 expression.
- In different colon cancer cell lines, antibody effectiveness correlated with tumour aggressiveness.
- In an in vivo nude mouse bearing human HCT 116 xenografts, tumour growth was inhibited by treatment with PrP antibody.
- 47 days after treatment, at 9 mg/kg antibody in combination with irinotecan, tumour sizes were approximately 33% smaller vs animals receiving irinotecan alone.
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