Alimentary TractTargeting cyclooxygenase 2 and HER-2/neu pathways inhibits colorectal carcinoma growth*,**
Section snippets
Cell culture and materials
All cell lines were purchased from the American Type Culture Collection except the HCA-7 rectal adenocarcinoma cell line, which was a kind gift of Susan Kirkland (ICRF, London, England).25 Cells were grown in Dulbecco's modified Eagle medium (DMEM) or McCoy medium (Life Technologies, Inc., Rockville, MD) supplemented with 10% fetal bovine serum (FBS; Hyclone, Logan, UT), L-glutamine (2 mmol/L), penicillin (100 U/mL), and streptomycin (100 μg/mL) in a 5% CO2 atmosphere with constant humidity.
Results
We first sought to identify a human colorectal cancer cell line that would serve as a good model system to study the biologic effects of both selective COX-2 inhibitors and anti–HER-2/neu antibodies. We have previously reported that the HCA-7 colorectal carcinoma cells express high levels of COX-2 and produce significant amounts of prostaglandins.32 Furthermore, selective COX-2 inhibitors block the growth of these cells both in vitro and in vivo. To determine whether this cell line was also a
Discussion
The impetus for a combination of therapeutic agents for cancer treatment lies in the realization that tumor cells have evolved to bypass multiple growth-control pathways.35 Thus, targeting any single pathway may not be sufficient to achieve a meaningful clinical effect. The rationale for combination targeting of the COX-2 and HER-2/neu pathways to inhibit colorectal cancer cell growth is derived from 2 major observations: (1) both the COX-2 and HER-2/neu pathways have been shown to play
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Address requests for reprints to: Raymond N. DuBois, M.D., Ph.D., Department of Medicine/GI, MCN C-2104, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2279. e-mail:[email protected]; fax: (615) 343-6229.
- **
Supported in part by grants DK 47297, P01CA77839, and P30CA-68485 from the United States Public Health Services (to R.N.D.), by a Veterans Affairs Research Merit Grant (to R.N.D.), and by the T. J. Martell Foundation and the National Colorectal Cancer Research Alliance (NCCRA).