Exploring the potential chemopreventative effect of aspirin and rofecoxib on hereditary nonpolyposis colorectal cancer-like endometrial cancer cells in vitro through mechanisms involving apoptosis, the cell cycle, and mismatch repair gene expression.
Women in hereditary nonpolyposis colorectal cancer (HNPCC) families have up to a 71% lifetime risk for developing endometrial cancer (EC). This compares to the female lifetime risk for colorectal cancer (CRC) in HNPCC of 60%. The basis of HNPCC is an inherited mutation in a mismatch repair gene (MMR). Aspirin and COX2 inhibitors seem to have a chemoprotective effect on CRC in the general population and are the subject of prospective clinical studies in patients at high risk for CRC including HNPCC. There is no evidence that these agents have any protective effect against EC in the general population. This study investigated the effect of aspirin and a COX2 inhibitor (rofecoxib) on an HNPCC EC cell line model (Ishikawa) by assessing the effect on proliferation, apoptosis, the cell cycle, and MMR gene expression. Aspirin inhibits EC cell proliferation by inducing apoptosis and changes in the cell cycle. This effect is not mediated by changes in MMR gene (hMSH2) expression as assessed by quantitative reverse transcription-polymerase chain reaction. Rofecoxib inhibits EC cell proliferation; this did not appear to be mediated by induction of apoptosis, by alterations of the cell cycle, or by changes in MMR gene expression.
Wood
N J
NJ
Department of Obstetrics and Gynaecology, St James' University Hospital, Leeds, United Kingdom.
Quinton
N A
NA
Burdall
S
S
Sheridan
E
E
Duffy
S R
SR
D017209:Apoptosis / Q000187:drug effects*; D001241:Aspirin / Q000627:therapeutic use*; D002277:Carcinoma / Q000473:pathology / Q000517:prevention & control*; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000473:pathology / Q000517:prevention & control*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D053843:DNA Mismatch Repair / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D016889:Endometrial Neoplasms / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007783:Lactones / Q000627:therapeutic use*; D013450:Sulfones / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D001241:Aspirin