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目的:研究三氧化二砷(As2O3)对人体外肠癌细胞HCT116的生长抑制作用和增殖周期的影响.方法:肠癌细胞HCT116进行体外培养后,分成对照组,0.5μmol/L As2O3组、1.5μmol/L As2O3组、2.5μmol/L As2O3组,在不同时间段内,MTT法观察不同浓度As2O3对肠癌细胞的生长抑制情况,绘制细胞生长曲线;流式细胞技术分析细胞增殖的周期变化.结果:MTT结果显示0.5μmol/L的低剂量A s2O3抑制率与对照组无明显差别(P>0.05),1.5μmol/L As2O3组抑制率和2.5μmol/L As2O3组抑制率与对照组相比较,组间均有差异(P<0.05),且As2O3对肿瘤细胞的抑制作用均随时间延长而增强,并在第3天时抑制作用最明显(1.5μmol/L As2O3组抑制率为38.64%±0.16%,2.5μmol/L As2O3组抑制率为51.42%±0.53%,对照组是8.35%±0.76%),然后第4天有下降的趋势,但2.5μmol/L As2O3的抑制作用第4天未见明显下降趋势(抑制率为52.93%±1.53%);流式细胞术分析表明,As2O3为0.5μmol/L时,S期细胞分布35.58%±0.63%(对照组25.69%±1.46%),G2/M期细胞分布33.41%±0.73%(对照组30.44%±1.51%)两者比较没有统计学差异(P>0.05),当As2O3浓度为1.5μmol/L时,S期细胞占42.69%±2.64%,G2/M期细胞占22.46%±0.59%,与对照组比较,差异有统计学意义(P<0.05);药物提高到2.5μmol/L时,S期细胞占45.71%±1.53%,G2/M期细胞占14.66%±0.92%,与对照组比较差异有统计学意义(P<0.05).结论:As2O3对人肠癌细胞HCT116具有明显的抑制作用,主要抑制肿瘤细胞DNA合成的增殖期,且至少1.5μmol/L以上的As2O3浓度才能达到抑制肿瘤增长繁殖的效果,所以临床应用As2O3进行肠癌化疗时应掌握好有效的剂量浓度和化疗时间窗,从而提高化疗效果的同时最大减轻不良反应,延缓耐药性的发生.
Objective: To study the effect of arsenic trioxide (As2O3) on the growth inhibition and proliferation of human colorectal cancer cell line HCT116.Methods: Human colorectal cancer cell line HCT116 was cultured in vitro and divided into control group, 0.5μmol / L As2O3 group, 1.5μmol / L As2O3 group and 2.5μmol / L As2O3 group, MTT assay was used to observe the growth inhibition of colorectal cancer cells with different concentrations of As2O3, and the cell growth curve was drawn.Flow cytometry was used to analyze the cell cycle changes.Results: MTT The results showed that there was no significant difference between the control and the low dose of 0.5μmol / L A s2O3 (P> 0.05). Compared with the control group, the inhibitory rate of 1.5μmol / L As2O3 and the inhibition rate of 2.5μmol / (P <0.05), and the inhibitory effect of As2O3 on tumor cells increased with time, and the most obvious inhibition was on the 3rd day (the inhibitory rate was 38.64% ± 0.16% in the 1.5μmol / L As2O3 group μmol / L As2O3, the inhibitory rate was 51.42% ± 0.53% in the control group and 8.35% ± 0.76% in the control group), and then decreased on the 4th day. However, the inhibitory effect of 2.5μmol / L As2O3 did not show a significant decrease on the 4th day (Inhibition rate was 52.93% ± 1.53%). Flow cytometry analysis showed that As2O3 was 0.5μmol / L , 35.58% ± 0.63% in S phase (25.69% ± 1.46% in control group), 33.41% ± 0.73% in G2 / M phase (30.44% ± 1.51% in control group), there was no statistical difference between the two groups (P> 0.05). When As2O3 concentration was 1.5μmol / L, cells in S phase accounted for 42.69% ± 2.64% and cells in G2 / M phase accounted for 22.46% ± 0.59%, which was significantly different from that in control group (P <0.05) (P <0.05) .Conclusion: When the drug is increased to 2.5μmol / L, the proportion of cells in S phase is 45.71% ± 1.53% and the cells in G2 / M phase are 14.66% ± 0.92% HCT116 human colorectal cancer cells have a significant inhibitory effect, the main inhibition of tumor cell DNA synthesis of proliferative phase, and at least 1.5μmol / L As2O3 concentration in order to achieve the effect of inhibiting tumor growth and reproduction, so the clinical application of As2O3 in colorectal cancer chemotherapy Should have a good dose of concentration and chemotherapy window, thereby enhancing the effect of chemotherapy while minimizing adverse reactions, delay the occurrence of drug resistance.