Effects of bafilomycin A1, a vacuolar type H+ ATPase inhibitor, on the thermosensitivity of a human pancreatic cancer cell line.
OBJECTIVE
It has been known that the thermosensitivity of tumour cells can be increased by lowering intra-cellular pH (pHi) by inhibiting pHi control mechanisms. The pHi is partially controlled by transport of H+ from cytoplasm into endocytic and secretary systems in the cells mediated by vacuolar type H+ATPase and also by transport of H+ through plasma membrane.


METHODS
This study investigated the effects the bafilomycine A1, an inhibitor of the vacuolar type H+ATPase and the EIPA, an inhibitor of the Na+/H+ exchanger in plasma membrane, on thermosensitivity of AsPC-1 cells, a human pancreatic cancer cell line. It also investigated the effects of combination of bafilomycine A1 and EIPA.


RESULTS
The treatment of cancer cells with bafilomycine A1 or EIPA individually slightly lowered pHi of the cells in vitro and increased the thermosensitivity of the cells.


CONCLUSIONS
The combination of these two drugs significantly lowered pHi and increased thermosensitivity of cancer cells in vitro and enhanced the heat-induced the growth delay of AsPC-1 tumours grown s.c in the legs of BALB/cA nude mice.
Hayashi
Yasuo
Y
First Department of Surgery, Faculty of Medicine, University of Fukui, Matsuoka, Fukui, Japan. yukiho@green.ocn.ne.jp
Katayama
Kanji
K
Togawa
Tamotsu
T
Kimura
Toshihisa
T
Yamaguchi
Akio
A
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D001833:Body Temperature Regulation / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D003131:Combined Modality Therapy; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006979:Hyperthermia, Induced; D018942:Macrolides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000503:physiopathology* / Q000628:therapy; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors; D014183:Transplantation, Heterologous / Q000473:pathology
D004791:Enzyme Inhibitors; D018942:Macrolides; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride; C040929:bafilomycin A1; D006180:Proton-Translocating ATPases; C039614:ethylisopropylamiloride