title: Proteomic differential display analysis for TS-1-resistant and -sensitive pancreatic cancer cells using two-dimensional gel electrophoresis and mass spectrometry.
abstract: TS-1 is an oral anticancer agent containing two biochemical modulators for 5-fluorouracil (5-FU) and tegafur (FT), a metabolically activated prodrug of 5-FU. TS-1 has been recognized as an effective anticancer drug using standard therapies for patients with advanced pancreatic cancer along with gemcitabine. However, a high level of inherent and acquired tumor resistance to TS-1 induces difficulty in the treatment. To identify proteins linked to the TS-1-resistance of pancreatic cancer, we profiled protein expression levels in samples of TS-1-resistant and -sensitive pancreatic cancer cell lines by using two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The cytotoxicity of a 5-FU/5-chloro-2,4-dihydroxypyridine (CDHP) combination towards pancreatic cancer cell lines was evaluated by MTS assay. Panc-1, BxPC-3, MiaPaCa-2 and PK59 showed high sensitivity to the 5-FU/CDHP combination (TS-1-sensitive), whereas PK45p and KLM-1 were much less sensitive (TS-1-resistant). Proteomic analysis showed that eleven spots, including T-complex protein 1 subunit beta, ribonuclease inhibitor, elongation factor 1-delta, peroxiredoxin-2 and superoxide dismutase (Cu-Zn), appeared to be down-regulated, and 29 spots, including hypoxia up-regulated protein 1, lamin-A/C, endoplasmin, fascin and annexin A1, appeared to be up-regulated in TS-1-resistant cells compared with -sensitive cells. These results suggest that the identified proteins showing different expression between TS-1-sensitive and -resistant pancreatic cancer cells possibly relate to TS-1-sensitivity. These findings could be useful to overcome the TS-1-resistance of pancreatic cancer cells.
authors: Department of Biochemistry and Functional proteomics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
authors: Kanako
authors: K
authors: Yoshida
authors: Yasuhiro
authors: Y
authors: Kuramitsu
authors: Kohei
authors: K
authors: Murakami
authors: Shomei
authors: S
authors: Ryozawa
authors: Kumiko
authors: K
authors: Taba
authors: Seiji
authors: S
authors: Kaino
authors: Xiulian
authors: X
authors: Zhang
authors: Isao
authors: I
authors: Sakaida
authors: Kazuyuki
authors: K
authors: Nakamura
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010094:Oxonic Acid / Q000008:administration & dosage; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D011725:Pyridines / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage
chemical_list: C417063:5-chlorodihydroxypyridine; D004338:Drug Combinations; D009363:Neoplasm Proteins; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D005472:Fluorouracil