Effect of fatty acid synthase inhibitor on growth and apoptosis of human gastric cancer cells

AIM: To investigate the effect of fatty acid synthase inhibitor-cerulenin on the growth and apoptosis of human gastric cancer cells. METHODS: The inhibitory effect of cerulenin was observed at 2.5, 5, 10, 20 and 40 mg/L on the growth of MKN28, SGC7901 and MKN45 cell lines in medium containing 100 mL/L fetal bovine serum and serum-free medium for 24 h by MTT assays. Flow cytometry (FCM) analysis and agarose gel electrophoresis were used to study the changes of cell apoptosis. RESULTS: Cerulenin caused dose-dependent inhibition on the growth of human gastric cancer cells MKN28, SGC7901 and MKN45; Inhibition was much greater in serum-free medium than in medium with 100mL/L fetal bovine serum. The inhibitory rates of MKN28 after 24 h exposure to cerulenin at 2.5, 5, 10, 20 and 40 mg/L in medium with fetal bovine serum medium and serum-free were 3,2 ± 0.6%, 7.3 ± 0,5%, 11.3 ± 0.7%, 17.7 ± 1.2%, 41.7 ± 1.0% and 5.1 ± 1.3%, 11.1 ± 1.7%, 20.9 ± 1.3%, 31.3 ± 2.3%, 60.2 ± 3.9%, respectively (1.4 ± 1.3%, 3.3 ± 2.0%, 6.2 ± 3.2%, 8.1 ± 1.1%, 10.1 ± 1.7% and 2.8 ± 1.1%, 6.1 ± 0.8%, 8.5 ± 1.3%, 11.5 ± 0.9%, 17.2 ± 2.2%, P <0.05 vs controls, respectively). The inhibitory rates of SGC7901 after 24 h exposure to cerulenin at 2.5, 5, 10, 20 and 40 mg/L in medium with fetal bovine serum and serum-free medium were 3.4 ± 0.8%, 9.5 ± 1.2%, 23.3 ± 1.7%, 38.5 ± 1.8%, 65.2 ± 2.1% and 6.6 ± 0.9%, 14.3 ± 2.1%, 33.0 ± 1.8%, 56.9 ± 2.2%, 78.2 ± 1.4%, respectively (2.3 ± 1.0%, 5.0 ± 1.2%, 7.3 ± 1.0%, 9.7 ± 1.9%, 13.4 ± 1.3% and 3.9 ± 1.2%, 8.7 ± 1.5%, 10.5 ± 1.9%, 13.8 ± 1.6%, 19.5 ± 1.7%, P <0.05 vs controls, respectively). The inhibitory rates of MKN45 after 24 h exposure to cerulenin at 2.5, 5, 10, 20 and 40 mg/L in medium with fetal bovine serum medium and serum-free were 5.9 ± 1.1%, 13.5 ± 0.9%, 30.5 ± 1.9%, 49.1 ± 1.5%, 71.7 ± 2.0% and 8.4 ± 1.1%, 19.6 ± 1.4%, 40.4 ± 1.4%, 67.0 ± 1.3%, 83.8 ± 2.0%, respectively (2.7 ± 1.4%, 7.4 ± 1.1%, 9.6 ± 1.3%, 12.6 ± 1.1%, 16. 7 ± 2.2% and 4.4 ± 1.6%, 9.5 ± 0.9%, 13.7 ± 0.7%, 18.4 ± 1.6%, 26.6 ± 2.1%, P <0.05 vs controls, respectively). After 24 h exposure to cerulenin, the IC50 of MKN28, SGC7901 and MKN45 cells in serum-free medium (13.3 mg/L, 16.7 mg/L, 32.3 mg/L, respectively) were lower than those of serum-medium group (20.1 mg/L, 26.6 mg/L, 46.3 mg/L, P <0.01). When MKN28, SGC7901 and MKN45 cells were treated for 12 h with 40 mg/L of cerulenin, the apoptotic rate revealed 10.1 ± 0.7%, 12.5 ± 0.4% and 14.9 ± 0.8%, respectively (P <0.01 vs controls) and resulted in a block in G2/M phase of the cell cycle of gastric cancer cells. DNA agarose gel electrophoresis showed the typical DNA ladder of apoptosis. CONCLUSION: Fatty acid synthase inhibitor- cerulenin inhibits the growth of human gastric cancer cells and induces apoptosis of human gastric cancer cells. Fatty acid synthase might be a potential target for anti-gastric cancer.

Duke Scholars

Author Fengming Chen Pathology