プロテオミクスによる薬剤耐性関連蛋白質の同定と治療への応用の可能性

概要

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While Gemcitabine (2'-deoxy-2'-difluorodeoxycytidine: Gemzar) (GEM) is thought to be most effective for pancreatic cancer, its clinical effects do not seem properly evaluated due to a high level of inherent and acquired resistance in the tumor cells. We analyzed GEM-resistant and GEM-sensitive human pancreatic cancer cell lines proteomically to identify the proteins related to the GEM-resistance. First, we separated cancer cell proteins by two-dimensional gel electrophoresis, and identified the protein spots whose expressions differed between GEM-sensitive and -resistant cell lines by liquid chromatography-tandem mass spectrometry (LC-MS / MS). It was recognized that heat shock protein 27 (HSP27) was high in GEM-resistant cell lines, and that KLM1-R cells, a cell line which has acquired resistance to GEM, restored sensitivity to it when HSP27 was knocked down by siRNA. These findings suggest that expression of HSP27 should be reduced in order that the antitumor effects of GEM may be well exerted. Since the expression of HSP27 was dramatically reduced in the KLM1-R cells treated with GEM and IFN-γ, improved therapeutic effects may be expected in the combination of IFN-γ with GEM.