目的：探讨三氧化二砷（As2 O3）联合紫杉醇（paclitaxel，PTX）对肺癌的治疗作用。方法噻唑蓝法（methyl thiazolyl tetrazolium，MTT）检测As2 O3联合PTX抑制肺癌A549细胞的增殖。采用激光共聚焦显微镜观察给药后对肺癌A549细胞的凋亡诱导作用。通过构建体外肿瘤球模型观察给药后对肿瘤球的生长抑制，模拟给药后药物在体内对肿瘤生长的抑制能力。建立肺癌裸鼠移植瘤模型，随机分为生理盐水组、As2 O3干预组、PTX干预组和联合干预组。每天分别用设定浓度的生理盐水、As2 O3、PTX、As2 O3＋PTX对移植瘤小鼠腹腔内注射给药。观察给药后肿瘤大小的变化，计算抑瘤率。对肿瘤切片分别采用苏木精-伊红染色法（hematoxylin-eosin staining，HE）进行染色，考察As2 O3、PTX、As2 O3＋PTX诱导体内肿瘤细胞凋亡的效果。结果肺癌A549细胞给药48 h后，生理盐水组、As2 O3干预组、PTX 干预组和联合干预组对肿瘤细胞的抑制率分别为（3.35±0.21）％、（47.55±2.25）％、（64.64±3.35）％和（84.58±3.76）％，各药物干预组与生理盐水组相比，差异的具有统计学意义（P＜0.01）。生理盐水组诱导肿瘤细胞早期凋亡率为0.26％，As2 O3干预组为9.7％，PTX干预组为17.8％，联合干预组为42.5％，而与生理盐水组、As2 O3干预组和PTX干预组相比，联合干预组能够增加肿瘤细胞早期凋亡率，差异具有统计学意义（P＜0.01）。肿瘤球给药7d后生理盐水组肿瘤球体积增大1.36倍，As2 O3干预组、PTX干预组和联合干预组分别使肿瘤体积减小到原体积的（77.35±2.31）％、（61.68±2.44）％和（44.85±3.34）％，差异均具有统计学意义（P＜0.01）。荷瘤裸鼠治疗实验以生理盐水组为对照，As2O3干预组、PTX干预组和联合干预组对肿瘤生长的抑制率分别为（22.4±4.5）％、（39.5±6.2）％和（69.5±7.3）％，联合干预组与其他组间差异具有统计学意义（P＜0.01）。结论As2 O3能够有效增强PTX 抑制A549细胞的增殖和裸鼠异位肿瘤的生长，As2 O3联合PTX 可能作为肺癌潜在有效的治疗手段。%Objective To evaluate the effect of As2O3 combined with paclitaxel(PTX)on the treatment of lung cancer.Methods The anti-proliferation efficiency of As2 O3 combined with PTX was evaluated by MTT assay.Tumor spheroids were used to evaluate anti-tumor ability of As2 O3 combined with PTX.Transmission electron microscope (TEM)were used to observe the apoptosis morphous.A549 cell were xenografted in mice to establish the animal model,and the nude mices were devided into four groups,saline group,As2 O3 group,PTX group and As2 O3 +PTX group.The animal model were used to evaluate the effect of anti-tumor.The tumor size of every group were measured.HE was used to observe the apoptosis of cancer cells. Results The cell inhibition rate of A549 cell were(3.35 ±0.21)%,(47.55 ±2.25)%,(64.64 ±3.35)%and(84.58 ±3.76)%after treatment with saline,As2O3,PTX and As2O3combined with PTX after 48h respectively(P<0.01).The early apoptosis rate of cancer cells were 0.26%,9.7%, 17.8% and 42.5% for saline group,As2 O3 group,PTX and As2 O3 +PTX group respectively(P<0.01 ).The final tumor spheroid volumes in saline group increased 1.36 times after 7 days.The final tumor spheroid volumes reduced to(77.35 ±2.31)%,(61.68 ±2.44)% and(44.85 ±3.34)% in As2O3,PTX and As2O3 combined with PTX group respectively(P<0.01).The inhibition of lung cancer in vitro demonstrated the inhibition rate of tumor growth compared with saline group were(22.4 ±4.5)%,(39.5 ±6.2)% and(69.5 ±7.3)% for As2O3,PTX and As2O3 +PTX,respectively(P<0.01 ).Conclusion As2 O3 combined with PTX can effectively inhibit the proliferation of A549 cells and ectopic tumor growth in nude mice and it may be a potentially effective treatment for lung cancer.
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