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目的探讨三氧化二砷(arsenic trioxide,ATO,As_2O_3)对宫颈癌Hela细胞裸鼠移植瘤体内作用及其机制。方法建立裸鼠宫颈癌移植瘤模型,用低浓度As_2O_3[2mg/(kg·d)],高浓度As_2O_3[[5 mg/(kg·d)],顺铂(DDP)[3 mg/(kg·d)1及0.9%NaCl腹腔连续给药10 d,观察移植瘤的生长情况和抑瘤率,药物对裸鼠体重、肝肾组织的影响。通过流式细胞仪检测瘤细胞凋亡率,应用免疫组化方法检测p38和Caspase-3的表达。结果低浓度As_2O_3高浓度As_2O_3及DDP组的抑瘤率分别为31.48%,33.61%和53.11%,高浓度As_2O_3和DDP组的抑瘤率与阴性对照组的差异有统计学意义(P<0.05),DDP组药物的毒副作用大。两种浓度As_2O_3引起的细胞凋亡率明显高于阴性对照组(P<0.05)。P-P38和Caspase-3蛋白在As_2O_3治疗组的表达明显高于阴性对照组(P<0.05),且二者呈正相关(r=0.5164,P=0.01)。结论 As_2O_3能明显抑制宫颈癌移植瘤的生长,且毒副作用明显小于DDP,其抑癌机制之一为诱导肿瘤细胞凋亡。
Objective To investigate the effect and mechanism of arsenic trioxide (ATO, As_2O_3) on human cervical cancer Hela cell xenografts in nude mice. Methods Cervical cancer xenografts model was established in nude mice. Low concentration of As 2 O 3 [2 mg / (kg · d)], high concentration of As 2 O 3 [[5 mg / (kg · d) · D) 1 and 0.9% NaCl were administered intraperitoneally continuously for 10 days to observe the growth and tumor inhibition rate of the xenografts and the effects of the drugs on body weight, liver and kidney of nude mice. The apoptosis rate of tumor cells was detected by flow cytometry. The expression of p38 and Caspase-3 was detected by immunohistochemistry. Results The inhibitory rates of As2O3 and DDP in low concentrations of As2O3 and DDP were 31.48%, 33.61% and 53.11%, respectively. The inhibition rate of As2O3 and DDP in high concentration group was significantly lower than that in negative control group (P <0.05) , DDP group of drugs side effects. Apoptosis rates induced by As 2 O 3 at two concentrations were significantly higher than those at negative control (P <0.05). The expression of P-P38 and Caspase-3 in As2O3-treated group was significantly higher than that in the negative control group (P <0.05), and the positive correlation was found between them (r = 0.5164, P = 0.01). Conclusion As 2 O 3 can significantly inhibit the growth of cervical cancer xenografts, and its side effects are much less than that of DDP. One of the mechanisms of its inhibition is to induce apoptosis of tumor cells.