Gemcitabine sensitizes pancreatic cancer cells to the CTLs antitumor response induced by BCG-stimulated dendritic cells via a Fas-dependent pathway.

BACKGROUND/OBJECTIVES: There are increasing evidences suggesting that chemotherapeutic agents can enhance the cytotoxic T lymphocytes (CTLs) antitumor effect, but the precise mechanism is not fully explained. This study aims to investigate whether gemcitabine (GEM) can sensitize pancreatic cancer cells to the CTLs antitumor response, and explore the potential mechanism.

METHODS

Cell counting kit-8 assays (CCK-8) were performed to determine the tumor cell proliferation. Flow cytometric analysis was conducted to analyze maturation of DCs and the expression of Fas. An Annexin V FITC Apoptosis Detection Kit was performed to detect tumor cell apoptosis. CytoTox 96 Nonradioactive Cytotoxicity assays were used to determine T cell-mediated tumor cell lysis.

RESULTS

First, it was demonstrated that Bacillus Calmette Guérin (BCG) could be used to induce effective CTLs antitumor response. Then, GEM inhibited the growth of SW1990 cells, induced apoptosis and upregulated the Fas expression even at a low concentration. When antagonistic anti-Fas mAb ZB4 was preincubated with GEM-treated SW1990 cells, the lysis induced by CTLs was reduced. Moreover, agonistic anti-Fas mAb CH11 induced more apoptosis of GEM-treated SW1990 cells.

CONCLUSION

Our results show that GEM sensitizes pancreatic cancer cells to the CTLs antitumor response, and the sensitization is associated with upregulation of Fas on pancreatic cancer cells.