新型多金属氧酸盐药物{BiW8O30}对肝癌SK-HEP-1细胞的抑制作用

目的： 研究新型多金属氧酸盐药物{BiW₈O₃₀}对体外培养的肝癌细胞的作用及其机制。方法： 体外培养人肝癌细胞SK-HEP-1，实验组分别给予50、100、200、400 μmol/L的{BiW₈O₃₀}药液，对照组给予正常培养液，培养24和48 h后检测相应指标。采用细胞增殖实验检测细胞存活率并计算{BiW₈O₃₀}对SK-HEP-1细胞的半数抑制浓度（IC₅₀）；细胞集落形成实验检测集落形成数；划痕实验检测划痕愈合率；Transwell实验检测侵袭细胞数变化；荧光染色分析药物对细胞凋亡的影响。结果： 与对照组比较，50、100、200、400 μmol/L的{BiW₈O₃₀}处理24 h后，SK-HEP-1细胞存活率分别降低了29.98%、51.29%、65.81%、83.59%（P<0.01），48 h后分别降低了31.57%、66.23%、81.88%、83.97%（P<0.01）；IC₅₀分别为24 h时（102.07±1.38）μmol/L，48 h时（74.68±0.91）μmol/L；50、100、200 μmol/L的{BiW₈O₃₀}处理2周后，SK-HEP-1细胞的集落形成数分别降低了28.57%、63.27%、90.82%（P<0.01）；50、100、200 μmol/L的{BiW₈O₃₀}处理24 h后，SK-HEP-1细胞的划痕愈合率分别降低了8.47%、70.59%、80.83%（P<0.01），48 h后分别降低了19.56%、65.98%、75.49%（P<0.01）；SK-HEP-1的侵袭细胞数在24 h后分别降低了27.74%、45.51%、68.77%（P<0.01），48 h后分别降低了47.03%、72.20%、84.07%（P<0.01）。荧光染色后观察发现{BiW₈O₃₀}处理后的肝癌细胞皱缩，细胞核固缩、碎裂，出现凋亡小体。结论： 新型多金属氧酸盐药物{BiW₈O₃₀}通过抑制肝癌SK-HEP-1细胞的增殖、集落形成、迁移和侵袭能力以及诱导细胞凋亡发挥体外抗肿瘤作用。

Inhibitory effects of a novel polyoxometalate drug{BiW8O30}on liver cancer SK-HEP-1 cells

OBJECTIVE: To explore the effects and mechanisms of action of a new polyoxometalate drug {BiW₈O₃₀} in liver cancer cells. METHODS: Human hepatocellular carcinoma cell line SK-HEP-1 was cultured and treated with 50,100,200 and 400 μmol/L {BiW₈O₃₀} solution,respectively. The control group was given normal culture medium. The corresponding indexes were detected after 24 and 48 h of culture. Cell proliferation assay was used to detect cell viability and half maximal inhibitory concentration (IC₅₀);cell colony formation experiment was used to detect number of colony formation;wound healing rate was detected by scratch test;Transwell assay was used to detect the number of invasive cells;the effect of drugs on apoptosis was analyzed by fluorescence staining. RESULTS: After treatment with 50,100,200,400 μmol/L {BiW₈O₃₀} for 24 and 48 h,the survival rate of SK-HEP-1 cells decreased by 29.98%,51.29%,65.81%,83.59% and 31.57%,66.23%,81.88%,83.97%,respectively (P<0.01),compared with the control group. In addition,IC₅₀ were (102.07±1.38) and (74.68±0.91) μmol/L,respectively. After 2 weeks of treatment with 50,100,and 200 μmol/L {BiW₈O₃₀},the number of colony formation of SK-HEP-1 cells decreased by 28.57%,63.27%,and 90.82%,respectively (P<0.01). After treatment with 50,100,200 μmol/L {BiW₈O₃₀} for 24 and 48 h,the scratch healing rate of SK-HEP-1 cells decreased by 8.47%,70.59%,80.83% and 19.56%,65.98%,75.49%,respectively (P<0.01),the number of invaded cells of SK-HEP-1 decreased by 27.74%,45.51%,68.77% and 47.03%,72.20%,84.07% (P<0.01). Observation after fluorescent staining revealed that the liver cancer cells treated with {BiW₈O₃₀} shrank,the nuclei shrank,fragmented,and apoptotic bodies appeared. CONCLUSION: The new polyoxometalate drug {BiW₈O₃₀} was toxic to SK-HEP-1 cancer cells in vitro by inhibiting the proliferation,colony formation,migration and invasion,and by inducing cell apoptosis.