Down-regulation of the human tumor antigen mucin by gemcitabine on the pancreatic cancer cell line capan-2.
The nucleoside analogue gemcitabine displays therapeutic effects mainly against breast, ovarian and pancreatic cancer. Mucin, encoded by the gene MUC1, is a well-established tumor antigen expressed on these tumors. Knowledge of possible effects of chemotherapeutic drugs on the level of mucin epitope expression is important for the design of clinical protocols combining chemo- and immunotherapeutic approaches. In this study, we determined the influence of gemcitabine on the mucin expression of the human pancreatic carcinoma cell line Capan-2. The cells were treated with three different concentrations (0.01 microg/ml, 0.1 microg/ml and 0.25 microg/ml) of gemcitabine or were left untreated and were analyzed after 24 hours, 3 and 5 days. Flow cytometric analysis showed a dose-dependent decrease of mucin expression on the cell surface which remained over 5 days. The strongest reduction of mucin expression was detectable 24 hours after application of the drug. The down-regulation of the tumor antigen mucin by gemcitabine might weaken an immune response against mucin-expressing tumors, which are under treatment with this chemotherapeutic drug.
Dorn
David C
DC
Clinic of Oncology and Hematology, Charité Campus Mitte, Schumannstr. 20/21, 10 117 Berlin, Germany.
Harnack
Ulf
U
Pecher
Gabriele
G
D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009077:Mucins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D009077:Mucins; D003841:Deoxycytidine; D000093542:Gemcitabine