A New Strategy for the Therapy of Pancreatic Cancer Invasion and Metastasis by Protease Inhibitor and Protein Pump Inhibitor Agents

Tetsuo Ohta, Hisatoshi Nakagawara, Hajime Arakawa, Fumio Futagami, Yuji Tsukioka, Hirohisa Kitagawa, Masato Kayahara, Takukazu Nagakawa, Istuo Miyazaki

Department of Surgery (II), School of Medicine, Kanazawa University

The potential for hepatic metastasis in nude mice was studied by the intrasplenic implatation method with three human pancreatic cancer cell lines, Capan-1, BxPC-3, and MIAPaCa-2, especially in relation to serine protease expression. The inhibitory effect of a protease inhibitor agent, FOY-305, on hepatic metastasis was also assessed. In addition, we examined these cell lines, for expression of he vacuolar type proton pump (V-type ATPase), and determined the effect of its inhibitor agent, bafilomycin A1, on the cancer cell invasion in vitro by chemoinvasion assay using a MATRIGEL invasion chamber. The potential for hepatic matastasis was well correlated with expression of trypsinogen I (cationic isoform) in these cell lines, and the incidence of metastasis was significantly decreased by FOY-305. In addition, the potential for invasion in vitro in these cell lines was also significantly suppressed by bafilomycin A1 . These findings suggest that pharmacologic inhibition of the activity of serine protease and V-type ATPase may be a new strategy for the therapy of pancreatic cancer invasion and metastasis.

Key words
pancreatic cancer, vacuolar-type H⁺-ATPase, bafilomycin A₁

Reprint requests
Tetsuo Ohta Department of Surgery (II), School of Medicine, Kanazawa University
13-1 Takara-mach, Kanazawa, 920 JAPAN

Accepted
November 15, 1995

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