三氧化二砷对人肺腺癌细胞的细胞毒作用及其机制

背景与目的:三氧化二砷(arsenictrioxide,As2O3)应用于急性早幼粒细胞性白血病(acutepromyelocyticleukemia,APL)的临床化疗已显示较好疗效。目前,已开展了将As2O3用于治疗胃癌、头颈部癌和食管癌等实体瘤的实验研究。本研究旨在探讨As2O3对人肺腺癌SPCA1细胞的毒性及其作用机制。方法:MTT法检测As2O3对SPCA1细胞的生长抑制作用;流式细胞术测定经不同浓度As2O3处理后的SPCA1细胞的细胞周期改变、凋亡相关蛋白Fas和Bcl-2阳性细胞百分率及细胞内钙离子(IECa2+)含量变化。结果:As2O3可显著抑制SPCA1细胞生长增殖,且呈剂量-效应关系(r=0.973,P<0.05),其IC50为8.56μmol/L;As2O3能显著增加Fas蛋白表达和IECa2+含量(P<0.05),并使细胞周期阻滞在G2/M期,但对Bcl-2表达无影响(P>0.05)。结论:As2O3对SPCA1细胞有显著的毒性作用,其机制可能与上调Fas表达和增加IECa2+含量及阻滞细胞周期有关。

Toxicity of arsenic trioxide to human lung adenocarcinoma cell line SPCA1 and its mechanism

BACKGROUND & OBJECTIVE: Arsenic trioxide (As2O3) showed good curative effect on acute promyelocytic leukemia (APL) in clinic. Now, As2O3 was used in experimental research of treating solid tumors,such as gastric cancer,head and neck tumors, esophageal cancer, etc. This study was to research the toxicity effect of As2O3 on human lung adenocarcinoma cell line SPCA1, and its mechanism. METHODS: MTT assay was used to observe inhibitory effect of As2O3 on proliferation of SPCA1 cells; cell cycle changes,apoptosis-associated proteins,Fas and Bcl-2,and intracellular calcium ions (IECa(2+)) content in SPCA1 cells treated with different doses of As2O3 were measured by flow cytometry. RESULTS: As2O3 inhibited proliferation of SPCA1 cells dramatically with a dosage-effect correlation (r=0.973,P< 0.05),its 50% inhibitory concentration (IC(50)) was 8.56 micromol/L. As2O3 enhanced Fas protein expression,and intracellular Ca(2+) content (P< 0.05),but didn't influence Bcl-2 protein expression (P >0.05). The cell cycle arrested in G2/M phase in SPCA1 cells treated with As2O3. CONCLUSION: As2O3 could inhibit the growth of SPCA1 cells in vitro, its mechanism is probably associated with the increased Fas expression and intracellular Ca(2+) content,and cell cycle arrest.