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: Kanako Yoshida, Yasuhiro Kuramitsu, Kohei Murakami, Shomei Ryozawa, Kumiko Taba, Seiji Kaino, Xiulian Zhang, Isao Sakaida, Kazuyuki Nakamura
• Journal: Anticancer research (Anticancer Res) Vol. 31 Issue 6 Pg. 2103-8 (Jun 2011) ISSN: 1791-7530 [Electronic] Greece
• PMID: 21737628 (Publication Type: Journal Article)

Chemical References

• 5-chlorodihydroxypyridine
• Drug Combinations
• Neoplasm Proteins
• Pyridines
• S 1 (combination)
• Tegafur
• Oxonic Acid
• Fluorouracil

Topics

• Adenocarcinoma (drug therapy, metabolism)
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Cell Line, Tumor
• Drug Combinations
• Drug Resistance, Neoplasm
• Electrophoresis, Gel, Two-Dimensional (methods)
• Fluorouracil (administration & dosage)
• Humans
• Mass Spectrometry (methods)
• Neoplasm Proteins (biosynthesis)
• Oxonic Acid (administration & dosage)
• Pancreatic Neoplasms (drug therapy, metabolism)
• Proteomics (methods)
• Pyridines (administration & dosage)
• Tegafur (administration & dosage)