Effects of bafilomycin A1, a vacuolar type H⁺ ATPase inhibitor, on the thermosensitivity of a human pancreatic cancer cell line

Abstract

Purpose: 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.

Conclusion: 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.

• Hyperthermia
• intra-cellular pH
• thermosensitivity
• vacuolar type H⁺ ATPase inhibitor
• pancreatic cancer cell