Flow cytometric bromodeoxyuridine/DNA analysis of hyperthermia and/or adriamycin for human pancreatic adenocarcinoma cell line Capan-2

Abstract

The effects of hyperthermia, adriamycin (ADM), and hyperthermia combined with ADM on pancreatic cancer cells were investigated from the viewpoint of cytokinetics using flow cytometric bromodeoxyuridine (BrdUrd)/DNA analysis. Human pancreatic adenocarcinoma cell line Capan-2 was used. The untreated cells could be clearly divided into G1, S, G2M phases on contour plots of BrdUrd/DNA distribution. After heat treatment at 41-43 degrees C, there was an accumulation of cells in the G2M phase which was correlated with the increase in temperature. After heat treatment at 44 or 45 degrees C, there was marked increase in non BrdUrd-labeled cells in the S phase. ADM caused no change in the percent of non BrdUrd-labeled cells in the S phase, even after treatment with a concentration of 1.0 micrograms/ml, though that concentration of ADM caused a marked increase in the percent of cells in the G2M phase. After hyperthermia combined with ADM, the accumulation of the G2M phase increased remarkably, and was significantly higher than that after each treatment alone (P less than 0.005); however, non BrdUrd-labeled cells in the S phase did not increase. In this study the synergistic effect of hyperthermia combined with ADM in increasing the percent of cells in the G2M phase could be observed by flow cytometry. The study illustrates the importance of performing in vitro flow cytometric BrdUrd/DNA analysis of combined therapy prior to the use of the combined therapy in patients.