Synergism between SLC6A14 blockade and gemcitabine in pancreactic cancer: A 1H-NMR-based metabolomic study in pancreatic cancer cells.

Synergism between SLC6A14 blockade and gemcitabine in pancreactic cancer: A 1H-NMR-based metabolomic study in pancreatic cancer cells. Biochem J. 2020 May 07;: Authors: Cai A, Zheng H, Chen Z, Lin X, Li C, Yao Q, Bhutia YD, Ganapathy V, Chen R, Kou L Abstract Gemcitabine is the first-line chemotherapy for pancreatic cancer. To overcome the often-acquired gemcitabine resistance, other drugs are used in combination with gemcitabine. It is well-known that cancer cells reprogram cellular metabolism, coupled with the upregulation of selective nutrient transporters to feed into the altered metabolic pathways. Our previous studies have demonstrated that the amino acid transporter SLC6A14 is markedly upregulated in pancreatic cancer and that it is a viable therapeutic target. α-Methyltryptophan (α-MT) is a blocker of SLC6A14 and is effective against pancreatic cancer in vitro and in vivo. In the present study, we tested the hypothesis that α-MT could synergize with gemcitabine in the treatment of pancreatic cancer. We investigated the effects of combination of α-MT and gemcitabine on proliferation, migration, and apoptosis in a human pancreatic cancer cell line, and examined the underlying mechanisms using 1H-NMR-based metabolomic analysis. These studies examined the intracellular metabolite profile and the extracellular metabolite profile separately. Combination of α-MT with gemcitabine elicited marked changes in a wide variety of meta...
Source: The Biochemical Journal - Category: Biochemistry Authors: Tags: Biochem J Source Type: research