Nakata B, Chung Y S, Yokomatsu H, Sawada T, Kubo T, Kondo Y, Satake K, Sowa M
First Department of Surgery, Osaka City University Medical School.
Jpn J Cancer Res. 1992 May;83(5):477-82. doi: 10.1111/j.1349-7006.1992.tb01952.x.
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.
从细胞动力学角度,运用流式细胞术溴脱氧尿苷(BrdUrd)/DNA分析方法,研究了高温、阿霉素(ADM)以及高温联合ADM对胰腺癌细胞的影响。采用人胰腺腺癌细胞系Capan-2。未处理的细胞在BrdUrd/DNA分布的等高线图上可清晰分为G1、S、G2M期。在41 - 43摄氏度热处理后,G2M期出现细胞积聚,且与温度升高相关。在44或45摄氏度热处理后,S期非BrdUrd标记细胞显著增加。即使使用1.0微克/毫升浓度的ADM处理,ADM也未引起S期非BrdUrd标记细胞百分比的变化,不过该浓度的ADM使G2M期细胞百分比显著增加。高温联合ADM处理后,G2M期的积聚显著增加,且明显高于单独每种处理后的情况(P小于0.005);然而,S期非BrdUrd标记细胞并未增加。在本研究中,通过流式细胞术可观察到高温联合ADM在增加G2M期细胞百分比方面的协同作用。该研究说明了在对患者使用联合治疗之前,对联合治疗进行体外流式细胞术BrdUrd/DNA分析的重要性。