In vivo modulation of cisplatin cytotoxicity by the cholecystokinin antagonist MK-329 in human pancreatic cancer xenografts.
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| Abstract |
We have previously reported that the cholecystokinin antagonist MK-329 (also known as L-364,718 or devazepide) synergistically enhances sensitivity to cisplatin (DDP) in MIA-PaCa2 human pancreatic cancer cells in tissue culture. In this study, we examined the ability of MK-329 to modulate DDP sensitivity in vivo using MIA-PaCa2 pancreatic cancer xenografts growing subcutaneously in athymic nude mice. Twenty-four hours after tumor inoculation, mice received either DDP intraperitoneally, MK-329 subcutaneously, both DDP and MK-329 or drug vehicles alone. Both DDP and MK-329 alone caused a reduction in the rate of tumor growth. The combination of DDP and MK-329 resulted in enhanced tumor growth delay compared to DDP or MK-329 treated mice. Although MK-329 alone was not nephrotoxic, the addition of MK-329 to DDP treatment resulted in a significant increase in weight loss and nephrotoxicity compared to mice treated with DDP alone; this was reflected by an increase in the plasma BUN levels. Although we believe that the enhanced anti-tumor effect of DDP/MK-329 combination therapy may be independent MK-329's capability to block CCK receptors, the role of CCK receptor blockade in potentiating DDP-induced nephrotoxicity less clear.
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| Authors | R Jamshidipour, E B Pinho, S B Howell |
| Journal | Anticancer research (Anticancer Res) 1994 Nov-Dec Vol. 14 Issue 6B Pg. 2611-6 ISSN: 0250-7005 [Print] Greece |
| PMID | 7872689 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.) |
| Chemical References |
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