Cell cycle regulation of human pancreatic cancer by tamoxifen. Ann Surg Oncol 1998 Jun;5(4):342-9
Date
06/26/1998Pubmed ID
9641456DOI
10.1007/BF02303498Scopus ID
2-s2.0-0031778287 (requires institutional sign-in at Scopus site) 20 CitationsAbstract
BACKGROUND: Clinical trials have suggested a survival advantage for selected patients with metastatic pancreatic cancer treated with tamoxifen. We sought to identify the molecular mechanism by which tamoxifen inhibits human pancreatic cancer cell (HPCC) growth.
METHODS: HPCCs were grown in tamoxifen and growth inhibition was determined by 3H-thymidine uptake and by the MTT assay; changes in cell viability were determined by cell counts. Cell cycle alterations were evaluated by FACS, and the induction of apoptosis was evaluated using the TUNEL assay. Total cellular RNA was isolated after tamoxifen treatment, and Northern blot analysis was performed for p21waf1.
RESULTS: Tamoxifen inhibited HPCC growth as measured by inhibition of 3H-thymidine incorporation and by the MTT assay. However, there was no decrease in the total number of viable cells after 6 days of treatment with 10 microM of tamoxifen and no evident apoptosis, confirming the absence of a cytotoxic effect. Cell cycle analysis revealed cellular arrest in the G0/G1 phase, which correlated with p21waf1 mRNA upregulation in response to tamoxifen treatment.
CONCLUSIONS: Tamoxifen inhibits HPCC growth by inducing G0/G1 arrest with an associated increase in p21waf1 mRNA expression. Tamoxifen is an effective inhibitor of HPCC growth in vitro and warrants further in vivo study.
Author List
Robinson EK, Grau AM, Evans DB, Smid CM, Chiao PJ, Abbruzzese JL, Grimm EAAuthor
Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Antineoplastic Agents, HormonalApoptosis
Cell Cycle
Cell Division
Cyclin-Dependent Kinase Inhibitor p21
Cyclins
Flow Cytometry
Gene Expression Regulation
Humans
Pancreatic Neoplasms
RNA, Messenger
RNA, Neoplasm
Tamoxifen
Tumor Cells, Cultured
