羟基喜树碱与热疗联合对胃癌细胞系体外增殖抑制作用的研究

THE SUPPRESSION EFFECT OF HYDROXYCAMPTOTHECINE COMBINED WITH HYPERTHERMIA ON HUMAN GASTRIC ADENOCARCINOMA CELL LINES IN VITRO

目的研究羟基喜树碱与热疗联合对2株胃癌细胞系SGC7901和BGC823细胞体外增殖的影响。方法使用MTT法测定细胞增殖,确定羟基喜树碱的工作浓度,并以该浓度进行化疗或与热疗联合,计算24h和48h时的细胞生存率,根据Veleriote法判断热化疗联合24h或48h的作用效果;24h时流式细胞仪检测BGC823细胞的凋亡情况。结果以24h时IC20～IC30的药物浓度作为试验的工作浓度,确定HCPT对2株细胞系的工作浓度均为3μg/mL。单纯43℃热疗60min在24h对2株细胞系均有抑制作用(P<0.05),在48h时没有显著的抑制作用。HCPT在24h时对SGC7901细胞有显著的抑制作用(P<0.01),与43℃热疗60min联合后在24h和48h时均有显著的抑制作用(P<0.01),HCPT3μg/mL与热疗联合作用24h或48h对SGC7901细胞的增殖抑制具有明显的协同作用。HCPT化疗或与热疗联合在24h和48h时均对BGC823细胞有显著的抑制作用(P<0.01),HCPT3μg/mL与热疗联合作用24h时对BGC823细胞的增殖抑制具有次加作用,在48h时呈明显的协同作用;24h时流式细胞仪检测BGC823细胞的凋亡情况发现,热疗组、HCPT化疗组和热化疗组细胞凋亡率均较对照组显著升高(P<0.05)。结论HCPT3μg/mL与43℃热疗60min联合在24h和48h时对SGC7901细胞的增殖抑制具有明显的协同作用;对BGC823细胞的增殖抑制在24h时呈次加作用,在48h时呈明显的协同作用,这可能与细胞凋亡的增多有关。

Objective To investigate the anticancer effect of HCPT combined with hyperthermia on human gastric adenocarcinoma cell lines SGC-7901 and BGC-823. Methods The working concentrations of HCPT against gastric cancer cell lines were determined by MTT assay that has been developed for quantitative evaluation of the proliferation of cells. Then hyperthermia and chemotherapy were used singly or concurrently and the cell survival rates were obtained at 24 h or 48 h. The anticancer effect was evaluated by Veleriote method. The apoptosis rates of BGC-823 were determined at 24 h by flow cytometric analyses. Results The concentrations were defined as those of IC20～IC30 at 24 h. They both turned out to be 3 μg/mL. 43 ℃ hyperthermia 60 min showed obvious inhibition to the two cell lines at 24 h (P<0.05), but it did not at 48 h. HCPT showed obvious inhibition to SGC-7901 at 24 h (P<0.01), and it did at 24 h and 48 h when it was combined with hyperthermia at 43 ℃ for 60 min (P<0.01). HCPT 3 μg/mL combined with hyperthermia showed obvious synergism to SGC-7901 at 24 h and 48 h. HCPT chemotherapy or hyperthermia both obviously inhibited the growth of BGC-823 at 24 h and 48 h(P<0.01). HCPT 3 μg/mL combined with hyperthermia showed subaddictive effect to BGC-823 at 24 h and obvious synergism at 48 h. According to flow cytometric analyses at 24 h, hyperthermia and HCPT singly or concurrently could obviously increase the apoptosis rates of BGC-823 (P<0.05). Conclusions HCPT 3 μg/mL combined with 43 ℃ hyperthermia 60 min showed obvious synergism to SGC-7901 at 24 h and 48 h. And HCPT 3 μg/mL combined with hyperthermia showed subaddictive effect to BGC-823 at 24 h and obvious synergism at 48 h. The synergism might relate to the increase of cell apoptosis rates.