title: Metabolic profiling of gemcitabine- and paclitaxel-treated immortalized human pancreatic cell lines with K-RASG12D.
abstract: The mechanisms of action of gemcitabine (GEM) and paclitaxel (PTX) have been well investigated, and shown to be the inhibition of DNA polymerase and polymerization of tubulin, respectively. Meanwhile, genomic research has revealed that mutations in the K-RAS oncogene occur in over 90% of pancreatic cancer. Oncogenic alteration rewires alternative metabolic pathways to satisfy the demands of growth. The K-RAS oncogene also has been shown to upregulate glycolysis and glutaminolysis. However, it is still unclear whether K-RAS independently plays a central role in controlling tumor metabolism. Here, we conducted a metabolomic analysis of a simple oncogenic K-RAS cell line model constructed using human telomerase catalytic subunit-immortalized human pancreatic epithelial nestin-expressing cell lines with and without K-RASG12D. We also investigated the effect of GEM and PTX on these cells. As a result, it was shown in the cell with K-RASG12Dthat the level of lactate was increased and glutamic acid, glutamine, and aspartic acid levels were decreased. In the nucleotide metabolism, GEM-treated cells showed metabolic changes, whereas these phenomena were not observed in PTX-treated cells. In conclusion, it was suggested that K-RASG12Dindependently modified tumor metabolism and the difference between GEM and PTX in the nucleotide metabolism was revealed.
authors.affiliation: Division of Gastrointestinal Oncology, Shizuoka Cancer Center.
authors.forename: Akiko
authors.initials: A
authors.lastname: Todaka
authors.forename: Rina
authors.initials: R
authors.lastname: Umehara
authors.forename: Keiko
authors.initials: K
authors.lastname: Sasaki
authors.forename: Masakuni
authors.initials: M
authors.lastname: Serizawa
authors.forename: Kenichi
authors.initials: K
authors.lastname: Urakami
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kusuhara
authors.forename: Ken
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yasui
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D011905:Genes, ras / Q000235:genetics*; D006019:Glycolysis; D006801:Humans; D055442:Metabolome; D009154:Mutation; D017239:Paclitaxel / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D017239:Paclitaxel; D000093542:Gemcitabine