Abstract 2009 Utilizing Alterations in Metabolism to Preferentially Target Pancreatic Cancer

Pancreatic cancer is an aggressive form of cancer associated with a low survival rate. Dysfunction of the mitochondrial and metabolic changes have been a hallmark of cancer. The objective of this study is to compare the metabolic differences in noncancerous vs. cancerous pancreatic cells and leverage those differences to preferentially kill the cancerous cells. Metabolism was characterized in three pancreatic cell lines (immortalized (H6C7), ductal carcinoma (Su.86.86), and adenocarcinoma (BxPC-3)) by measuring succinate dehydrogenase (SDH) enzyme activity, glucose consumption, and ATP levels. Expression of L-2-hydroxyglutarate dehydrogenase (L2HGDH) as a marker of metabolism was also determined by RT-PCR. Survival of pancreatic cells treated with a glycolysis inhibitor, 2-deoxy-D-glucose (2DG), in combination with an SDH inhibitor, boscalid, was measured via clonogenic survival. We determined that the pancreatic ductal carcinoma cells (Su.86.86) showed the most metabolic activity which correlated with marked sensitivity to treatment with 2DG. The pancreatic adenocarcinoma cells (BxPC-3) exhibited an intermediate increase in metabolism and was killed synergistically with 2DG and boscalid. Our studies show that pancreatic cancer cells are preferentially killed by inhibitors of metabolism, while the immortalized, nontransformed pancreatic cells (H6C7) were not significantly affected. These results offer a new insight on possible treatments for pancreatic cancer that take advantage of metabolic pathways. Bemidji State University's biology research is graciously funded by Lueken's Cancer Scholars, Beitzel Student Research Fund, and Bemidji State University New Faculty Grant.