温热化疗对胃、结肠癌细胞的体外作用研究  

Effects of Hyperthermic Chemotherapy on Gastrointestinal Cancer Cells in Vitro

作　　者：孙跃民[1] 傅军[2] 张伟[2] 郑朝旭[1] 黄常志[3] 袁兴华[1] 

机构地区：[1]中国协和医科大学中国医学科学院肿瘤医院腹外科,北京100021 [2]中国协和医科大学中国医学科学院肿瘤研究所生物检测中心,北京100021 [3]中国协和医科大学中国医学科学院肿瘤研究所生化室,北京100021

出　　处：《癌症》2006年第8期974-978,共5页Chinese Journal of Cancer

摘　　要：背景与目的:术中腹腔内温热灌注化疗尚缺乏有力的基础研究依据,所设参数不统一,使研究缺乏可比性。本研究探讨温热化疗对胃、结肠癌细胞的体外作用,系统探讨温热化疗的影响因素。方法:MTS-PMS比色法检测不同药物、处理温度和时间对人胃癌细胞MGC-803和结肠癌细胞HCT-116增殖抑制作用;显微镜观察温热化疗对细胞形态的影响。结果:氟尿嘧啶(5-fluorouracil,5-FU)、丝裂霉素(mitomycin,MMC)、顺铂(cisplatin,DDP)和吡柔比星(pirarubicin,THP)对MGC-803和HCT-116细胞的杀伤作用,均具有较强的温度依赖关系,其作用在41℃～45℃温度区间内随温度升高而加强,45℃时,对MGC-803细胞的抑制率分别达到61.7%、79.2%、88.7%、94.7%,对HCT-116细胞的抑制率分别达到76.4%、78.7%、77.8%、91.7%,与不加药组相比,差异具有显著性(P<0.01)。THP在各个温度点的杀伤作用均高于其它3种常用温热化疗药物(P<0.01)。药物对HCT-116细胞的杀伤作用具有时间依赖关系,随处理时间的延长,药物杀伤作用增强;其中,43℃时药物作用在90min后逐渐进入平台期,此时4种药物的抑制率分别达到58.2%、72.8%、76.2%、92.3%。5-FU、MMC、DDP45℃作用45min强于43℃作用90min。THP在确定温度的各个时点的杀伤作用均强于其它受试药物(P<0.01)。显微镜观察表明,单纯温热和温热化疗协同均有一定的细胞杀伤作用,而热化疗组出现大量的死亡细胞。结论:DDP、MMC在43℃～45℃条件下具有较好的肿瘤杀伤效果,考虑到临床的实际条件,处理时间以60min为宜。与5-FU、DDP、MMC相比,THP对胃、结肠癌细胞具有更好的温热协同效应和肿瘤杀伤效果,具有进一步临床研究的价值。BACKGROUND ＆ OBJECTIVE： Little evidence is known from experimental research for intraoperative hyperthermic intraperitoneal chemotherapy. This study was to investigate the effect of hyperthermic chemotherapy on gastrointestinal cancer cells in vitro and explore the possible factors which may affect this method. METHODS： Gastric cancer cell line MGC-803 and intestinal cancer cell line HCT-116 were chosen. Cells were treated with different drugs, temperatures and duration. Cell viability and growth were measured by MTS-PMS assay. The morphology of the cells was observed under a microscope. RESULTS： Significant synergistic effect was observed when the two cancer cell lines were treated with 5-FU, MMC, DDP and THP in combination with elevated hyperthermia from 41℃ to 45℃ compared with control group （P〈0.01）. The strongest effect was achieved at 45℃, which the inhibitory effects of these four drugs were 61.7%, 79.2%, 88.7%, 94.7% on MGC-803 and 76.4%, 78.7%, 77.8%, 91.7 on HCT-1116, respectively. The inhibitory effect demonstrated a time and dose-dependent manner in HCT-116 cells within a certain period of time. The effect revealed a flat curve after 90 min when HCT-116 was treated with 43℃. THP had the strongest effect at any conditions among all tested drugs （P〈0.01）. Either simple thermotherapy or chemohyperthermia displayed considerable killing effects on cancer cells which were confirmed by microscope observation. And a great deal of dead cells were observed when treated with chemohyperthermia. CONCLUSIONS： DDP or MMC reveals relatively satisfactory antitumor effects with the optimal temperature of 43-45℃. Taken practical application into consideration, 60 min may be selected in clinical use. Synergistic antitumor effects of THP in combination with hyperthermia were prior to 5-FU, DDP or MMC, which deserve further clinical research.

关 键 词：胃肿瘤 结肠肿瘤 化学疗法 温热效应 MGC-803细胞 HCT—116细胞 

分 类 号：R735[医药卫生—肿瘤]