Full Length Research Paper
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.
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