In vitro thermochemotherapy of human colon cancer cells with cis-dichlorodiammineplatinum(II) and mitomycin C.

Abstract

The thermosensitivity of human colon adenocarcinoma (LoVo) cells was investigated as a function of temperature and duration of heating in exponentially growing cultures. At 39-43 degrees, time-dependent survival followed a simple exponential function. Do values decreased progressively with a rise in temperature, from Do at 40 degrees = 38 hr to Do at 42 degrees = 17 hr to Do at 43 degrees = 1.5 hr. thus indicating relative thermoresistance of LoVo cells compared to Chinese hamster ovary cells. Dose-dependent 1-hr survival of LoVo cells treated with cis-dichlorodiammineplatinum(II) and mitomycin C was effectively modified when treatment was conducted under hyperthermic conditions. For both agents and cultures in exponential and stationary growth phases, hyperthermia abolished the initial shoulder portion and steepened the subsequent exponential part of the survival curves for dose-modifying factors at the 10% survival level of 1.5 to 2.0 at 41 degrees and 2.6 to 2.8 at 42 degrees. This significant enhancement of drug-induced cell kill by moderate hyperthermia suggests that thermochemotherapy with mitomycin C and cis-dichlorodiammineplatinum(II) should be tested clinically with both regional and total-body hyperthermia.