Abstract

5-Fluorouracil (5-FU) is not well tolerated by some patients, because of its severe side effects. The aim of the present study was to investigate the effect of parthenolide (PTL) in augmenting the anti-tumor effect of 5-FU in gastric cancer cells KATO III and to determine if parthenolide can be used to decrease the dose of 5-FU. The mechanism underlying the anti-tumor effects of 5-FU was also investigated. Using flow cytometry, we analyzed apoptosis of KATO III cells. Growth proliferation of the cell line was assayed by MTT. PGE₂protein level was detected by ELISA and western blot analysis was used to detect the expression of the NF-κB/p65, COX-2, caspase-3 and caspase-9 proteins. We found that either 5-FU or PTL alone induced apoptosis of KATO III cells in a concentration-dependent manner; however, combined treatment with both 5-FU and PTL significantly improved apoptosis. MTT data demonstrated that KATO III cells were more sensitive to 5-FU treatment in the presence of PTL. The combination of 5-FU with PTL also resulted in a significant reduction of PGE₂ secretion, compared with the control. Expression of NF-κB/p65 and COX-2 was inhibited, whereas, caspase-3 and caspase-9 protein were upregulated. In conclusion, it is rational to include the NF-κB inhibitor PTL in regular 5-FU-based chemotherapy, which may not only allow a reduction in the dose of 5-FU to prevent adverse effect, but also enhance the chemotherapeutic effect of 5-FU in gastric cancer.

Key words: Parthenolide, 5-fluorouracil, gastric cancer, apoptosis, nuclear factor-kappa B.