Background: Resistance of colon cancer cells to FasR-mediated apoptosis due to loss of Fas receptors and overepression of Fas-associated phosphatase-1 (FAP-1) contributes to their evasion from immune attack by CTLs and NK cells. Therefore, we investigated the effects of recombinant IL-2 on FasR and FAP-1 expression of colon cancer cells, and its influence on the sensitivity of colon cancer cells to FasR-mediated apoptosis.
Methods: Colon cancer cell lines SW480, HT-29 and CaCo2 were incubated with IL-2 for different periods of time. Sensitivity of the cells to FasR-mediated apoptosis was assessed by measuring their apoptosis after treated with agonistic anti-FasR MAb CH-11. Additionally, Fas receptor levels were examined by immunofluorescence and mRNA expression of FasR and FAP-1 was investigated by RT-PCR.
Results: IL-2 incubation increased CH11-induced apoptosis in all colon cancer cell lines in a time-dependent manner (P < 0.05). In parallel, IL-2 up-regulated Fas receptor expression on HT-29 and CaCo2 cells at both protein and mRNA levels (P < 0.05), which were low before treatment, while high expression of FasR on SW480 cells remained unchanged. Additionally, IL-2 down-regulated FAP-1 mRNA expression on SW480 and CaCo2 cells, which was high before treatment (P < 0.05). However, low expression of FAP-1 on HT-29 cells remained stable after IL-2 treatment.
Conclusion: IL-2 enhances susceptibility of colon cancer cells to FasR-mediated apoptosis by up-regulating Fas receptor levels and by down-regulating FAP-1 expression, which accounts for its therapeutic effects on abolishing immune evasion in colon cancer cells.