title: Tamoxifen enhances the cytotoxicity of conventional chemotherapy in esophageal adenocarcinoma cells.
abstract: BACKGROUND
  Esophageal adenocarcinoma is a lethal malignancy which is increasing in incidence, and many patients receive chemotherapy as part of their treatment. We have previously demonstrated that esophageal adenocarcinoma-derived cell lines respond to treatment with estrogen receptor modulators, such as tamoxifen. Reports from breast cancer suggest that tamoxifen may attenuate the efficacy of other chemotherapeutic agents. We have therefore assessed the response of esophageal adenocarcinoma cell lines to tamoxifen therapy when given in combination with conventional agents.
  
  
  METHODS
  Two estrogen receptor (ER)-positive esophageal adenocarcinoma cell lines (OE-19 and OE-33) were treated with combinations of tamoxifen, cisplatin and 5-fluorouracil (5-FU). Effects on cell viability were measured using an MTS assay, and cell death was detected with annexin V/propidium iodide flow cytometry. To assess whether the efficacy of tamoxifen in these cell lines might be relevant to the clinical setting, we analyzed ER status in 10 esophageal adenocarcinoma tissue specimens by immunohistochemistry.
  
  
  RESULTS
  IC50 values (μM) for OE-19 and OE-33 were 11.2 and 7.1 for tamoxifen, 19.6 and 4.7 for cisplatin, and 1.7 and 5.9 for 5-FU, respectively. Cell death was detected in 11.9% and 15.8% of cells treated with tamoxifen, 7.9% and 8.7% cells treated with cisplatin, and 3.6% and 8.6% cells treated with 5-FU at their IC50s. The addition of tamoxifen to cisplatin increased cell death by 11.4% in OE-19 (p < 0.0001) and 16.3% in OE-33 (p < 0.0001). Similarly, the addition of tamoxifen to 5-FU increased cell death by 11.6% in OE-19 (p < 0.0001) and 15.9% in OE-33 (p < 0.0001). Eight of 10 tissue specimens showed positive staining for ERα and 7 of 10 for ERβ.
  
  
  CONCLUSIONS
  In a cell culture model the addition of tamoxifen to conventional chemotherapy appears to be both feasible and beneficial. Expression of ERα and ERβ was also confirmed in esophageal adenocarcinoma tissues.
authors: Flinders University Department of Surgery and Flinders Centre for Cancer Prevention and Control, Flinders Medical Centre, Adelaide, South Australia, Australia.
authors: S L
authors: SL
authors: Due
authors: Flinders University Department of Surgery and Flinders Centre for Cancer Prevention and Control, Flinders Medical Centre, Adelaide, South Australia, Australia.
authors: D I
authors: DI
authors: Watson
authors: Flinders University Department of Surgery and Flinders Centre for Cancer Prevention and Control, Flinders Medical Centre, Adelaide, South Australia, Australia.
authors: I
authors: I
authors: Bastian
authors: Flinders University Department of Surgery and Flinders Centre for Cancer Prevention and Control, Flinders Medical Centre, Adelaide, South Australia, Australia.
authors: G Q
authors: GQ
authors: Ding
authors: Flinders University Department of Surgery and Flinders Centre for Cancer Prevention and Control, Flinders Medical Centre, Adelaide, South Australia, Australia.
authors: O A
authors: OA
authors: Sukocheva
authors: Department of Anatomical Pathology, Flinders Medical Centre, Adelaide, South Australia, Australia.
authors: D St J
authors: DS
authors: Astill
authors: Flinders University Department of Surgery and Flinders Centre for Cancer Prevention and Control, Flinders Medical Centre, Adelaide, South Australia, Australia.
authors: L
authors: L
authors: Vat
authors: Flinders University Department of Surgery and Flinders Centre for Cancer Prevention and Control, Flinders Medical Centre, Adelaide, South Australia, Australia. Electronic address: damian.hussey@flinders.edu.au.
authors: D J
authors: DJ
authors: Hussey
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D004357:Drug Synergism; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism*; D013629:Tamoxifen / Q000008:administration & dosage; D014407:Tumor Cells, Cultured
chemical_list: D011960:Receptors, Estrogen; D013629:Tamoxifen; D002945:Cisplatin; D005472:Fluorouracil
keywords: Antineoplastic agents; Esophageal neoplasms; Estrogen receptors; Selective estrogen receptor modulators