Influence of anti-tumor drugs on immune escape and counterattack of colon cancer cells / 中国药理学通报

ABSTRACT

AIM Fas system plays an important role in the mechanism of immune escape and counterattack of colon cancer cells. This study was to investigate the influence of anti-tumor drugs on Fas, Fas ligand expressions on colon cancer cells. METHODS MTT method was used to get the inhibition concentration 50%(IC_ 50 ) of 5-fluorouracil (5-Fu), mitomycin (MMC), cisplatin (CP) to SW480. The concentrations of anti-tumor drugs were 0, 0.5 IC_ 50 , IC_ 50 , 2 IC_ 50 , respectively. Immmunocytochemical staining and flow cytometry analysis were used to detect the expression rates of Fas and FasL on SW480 cells before and after 5-Fu, MMC, CP treatments. In situ hybridyzation was used to observe Fas, FasL mRNA in SW480 cells before and after treatments. RESULTS IC_ 50 of 5-Fu, MMC, CP to SW480 were 11.70, 3.12, 3.40 mg?L -1 , respectively. Both immmunocytochemical staining and flow cytometry analysis found that without drug treatments SW480 expressed high FasL and low Fas, after the treatment of 5-Fu, Fas expression rates on SW480 increased but FasL remained unchanged; both Fas and FasL increased after the treatment of MMC or CP. In situ hybridization showed that after the treatment of 5-Fu and Fas mRNA on SW480 increased while FasL mRNA remained unchanged; both Fas mRNA and FasL increased after the treatment of MMC or CP. CONCLUSION Anti-tumor drugs can change the expression of Fas system on SW480 cells in different ways. MMC and CP can increase the sensitivity of colon cancer cells to apoptosis signals; at the same time, they possibly facilitate immune escape of tumor cells. However, 5-Fu does not have influence on immune escape of colon cancer cells. The target point is at the level of transcription or above it.-