乙烷硒啉对小鼠体内移植性肝癌(H_(22))和Lewis肺癌的抗肿瘤作用

The anti-tumor effect of ethaselen on transplanted liver cancer(H_(22)) and Lewis lung cancer mice

目的观察乙烷硒啉对小鼠移植性肝癌(H22)和Lewis肺癌的抗肿瘤作用,并探讨其可能的抗肿瘤机制。方法建立小鼠体内移植性肝癌(H22)和Lewis肺癌模型,每种属60只,分别设为5组:阴性对照、阳性对照(CTX)和乙烷硒啉3个剂量组,每组12只。于接种肿瘤第2天至第8天5组分别连续腹腔注射5g/L羧甲基纤维素钠溶液、60mg/kgCTX及25、12.5、6.3mg/kg乙烷硒啉。停药3d后(第11天)每组处理一半动物,计算抑瘤率,并用流式细胞仪观察其对细胞周期的影响;另一半动物观察生命延长率。结果乙烷硒啉在25、12.5、6.3mg/kg剂量下对小鼠肝癌H22移植瘤的抑瘤率分别为52.5%、43.6%和30.2%,生命延长率分别为56.6、38.7%和14.2%;对小鼠Lewis肺癌的抑瘤率分别为43.8%、29.6%和18.9%,生命延长率分别为47.3%、17.9%和6.3%。乙烷硒啉各剂量组肿瘤细胞凋亡率明显高于对照组(P<0.05),且25.0mg/kg组出现S期阻滞(P<0.05)。结论乙烷硒啉对小鼠移植性肝癌(H22)和Lewis肺癌具有抗肿瘤作用,且随剂量的增加其抑制肿瘤作用显著增强。其抗肿瘤作用可能是通过诱导细胞凋亡,同时干扰肿瘤细胞生长周期,导致S期阻滞而实现的。

Objective To observe the anti-tumor effect of ethaselen on transplanted liver cancer （H22） and Lewis lung cancer mice. Methods The transplanted liver cancer （H22） and Lewis lung cancer mice models were established. Each genus consisted of 60 mice, which were divided into control, CTX, and three ethaselen dose groups, respectively, with 12 mice in each. Intraperitoneal injection （ip.） of three dosages was performed once a day through the abdominal wall separately, from the second to the eighth day after cancer was transplanted. On the eleventh day, six mice in each group were killed to calculate the tumor inhibition ratio and observe the cell cycle by flow cytometry, and the others were observed for the life extension ratio. Results When ethaselen was given at the dosage of 25, 12.5 and 6.3 mg/kg, the tumor inhibition ratio was 52.5%, 43.6% and 30.2%, and the life extension ratio was 56.6%, 38.7% and 14.2% in the transplanted liver cancer （H22） mice, respectively. The tumor inhibition ratio was 43.8%, 29.6% and 18.9%, and the life extension ratio was 47.3%, 17.9% and 6.3% in the transplanted Lewis lung cancer mice, respectively. Compared with that of the control, the apoptosis ratio was obviously increased in each group, and there was obviously induced S phase arrest in 25.0 mg/kg （P〈0.05）. Oonclusion Ethaselen has an anti-tumor effect on the transplanted liver cancer （H22） and Lewis lung cancer mice, and as dosage is increased, the effect is enhanced. The mechanism may be accomplished through interfering tumor cell growth cycle, S phase arrest and apoptosis.