Effect of CD95 system in the pancreatic cancer cells sensitivity to chemotherapy / 中华消化杂志

ABSTRACT

Objective To explore the role of CD95 system in chemotherapeutic sensitivity of pancreatic cancer cells, in an attempt to enhance the efficacy of chemotherapy by transfection CD95 gene, and to provide the evidence for the immunological treatment of pancreatic cancer. Methods CD95 gene was transfected into the pancreatic cancer cell line SW1990 by lipofectamine. The transfected cells were selected by G418. CD95 expressions of the transfected cells were detected by Northern blot and Western blot. MTT assay was used to analyze the response of the transfected cells to 5 fluorouracil, adriamycin (ADM), gemcitabine and in combination with anti CD95 monoclonal antibody (mAb). The drug induced apoptosis of transfected cells was measured by flow cytometry. Results The transfected pancreatic cancer cell SW1990 could overexpress CD95 stably. The CD95 mRNA and protein expressions were significantly increased in the transfected cells than in the controls. Anti CD95 mAb could inhibit the growth of the transfected cells. In addition, transfected cells were more sensitive to clinically relevant concentrations of chemotherapeutic drugs than non transfected cells. Anti CD95 mAb addition could enhance the cytotoxic effect of chemotherapeutic drugs. Drug induced apoptosis in ADM treated transfected cells more pronounced than in non transfected cells. Conclusions CD95 transfection could increase the sensitivity of pancreatic cancer cell SW1990 to, and partly reverse the resistance to, chemotherapeutic drugs. The combination of chemotherapeutic drugs with anti CD95 mAb showed a synergistic cytotoxicity to pancreatic cancer cells.