Combined gamma-tocotrienol and erlotinib/gefitinib treatment suppresses Stat and Akt signaling in murine mammary tumor cells.

Abstract

BACKGROUND:

Heterodimer cooperation between ErbB receptors has limited clinical usefulness of receptor tyrosine kinase inhibitors (TKIs), erlotinib and gefitinib in the treatment of cancer. However, combination treatment of TKIs with gamma-tocotrienol targets multiple ErbB receptors and significantly inhibit +SA murine mammary tumor cell growth.

MATERIALS AND METHODS:

Cell proliferation was determined by tetrazolium (MTT) assay and immunofluorescent Ki-67 staining. Western blot analysis was used to determine treatment effects on epidermal growth factor (EGF)-dependent mitogenic signaling.

RESULTS:

Combined treatment of 3 microM gamma-tocotrienol with 0.25 microM erlotinib or 0.5 microM gefitinib significantly inhibited +SA cell growth and reduced cyclin D1 and phosphorylated (active) Pdk-1, Akt, Stat3 and Stat5 levels.

CONCLUSION:

Combined treatment of gamma-tocotrienol with erlotinib or gefitinib prevents ErbB receptor heterodimer cooperation and inhibits EGF-dependent mitogenic signaling in +SA murine mammary tumor cells. These findings strongly suggest that combination treatment may significantly improve therapeutic responsiveness in breast cancer patients.

• Authors: Sunitha V Bachawal, Vikram B Wali, Paul W Sylvester
• Journal: Anticancer research (Anticancer Res) Vol. 30 Issue 2 Pg. 429-37 (Feb 2010) ISSN: 1791-7530 [Electronic] Greece
• PMID: 20332450 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Chromans
• Quinazolines
• STAT Transcription Factors
• Vitamin E
• plastochromanol 8
• Erlotinib Hydrochloride
• Proto-Oncogene Proteins c-akt
• Gefitinib

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Blotting, Western
• Cell Proliferation (drug effects)
• Chromans (pharmacology)
• Erlotinib Hydrochloride
• Female
• Gefitinib
• Mammary Neoplasms, Animal (drug therapy, metabolism, pathology)
• Mice
• Proto-Oncogene Proteins c-akt (metabolism)
• Quinazolines (administration & dosage)
• STAT Transcription Factors (metabolism)
• Signal Transduction (drug effects)
• Vitamin E (analogs & derivatives, pharmacology)