期刊
ANTICANCER RESEARCH
卷 38, 期 12, 页码 6683-6689出版社
INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.13036
关键词
Pancreatic cancer; PANC-1; glutamine; fatty acid; acetyl-CoA carboxylase
类别
资金
- Japan Society for the Promotion of Science (JSPS), Japan [17K08429]
Background/Aim: Acetyl-CoA carboxylase (ACC) is a rate-limiting enzyme in fatty acid synthesis. In this study, we investigated the effect of ACC inhibition on survival of pancreatic cancer cells. Material and Methods: AsPC-1, BxPC-3 and PANG-1 were used as human pancreatic cancer cell lines. 5-(etradecyloxy)-2-furoic acid (TOFA) and bis-2(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES) were used as inhibitors of ACC and glutaminase (GLS) respectively. Apoptotic and live cells were distinguished by annexin-V staining. The activity of caspase-3 was evaluated by measuring the fluorescence intensity of the degradation product of the substrate, N-acetyl-Asp-Glu-Val-Asp-7-amido-4trifluoromethylcoumarin. Results: TOFA increased the number of annexin V-positive cells and enhanced caspase-3 activity in AsPC-1 and BxPC-3, but not in PANG-1 cells. The number of PANG-1 cells increased after 48 h in Earle's balanced salt solution. Interestingly, proliferation of PANG-1 cells was drastically suppressed by glutamine deprivation, but not by inhibition of glycolysis. BPTES also induced cell death to the same extent as glutamine deprivation. In addition, TOFA induced cell death of PANG-1 cells, both in the presence of BPTES and with glutamine deprivation, suggesting that inhibition of glutaminolysis causes cell death and enhances the effect of TOFA in PANG-1 cells. Conclusion: These findings suggest that glutaminolysis is important for the survival of pancreatic cancer cells showing tolerance to nutrient starvation such as PANG-1 cells, and use of a combination of inhibitors of ACC and GLS may be a new strategy for treatment of pancreatic cancer.
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