自由基诱发剂对大肠癌细胞脂质过氧化、膜脂流动性及DNA含量的影响

Effects of oxy-radical on lipid peroxidation,membrane fluidity and DNA content of cancer cells

本文以体外培养的大肠癌细胞为模型，观察了自由基诱发剂ｔｂｏｏＨ及抗癌药物对癌细胞脂质过氧化、膜脂流动性及ＤＮＡ含量的影响。结果表明，作用早期ＬＰＯ含量即有明显增加，且随温育时间的延长而增强，但早期ＤＮＡ含量则无明显变化，提示细胞ＬＰＯ含量的变化出现于细胞核酸ＤＮＡ改变之前。ｔｂｏｏＨ结合５－ＦＵ作用于癌细胞，发现在早期ＤＮＡ便可出现抑制作用，提示细胞膜的脂质过氧化损伤可增强抗癌药物的作用。采用ＤＰＨ荧光探针标记观察了细胞脂质过氧化与膜脂流动性的关系，结果表明ｔｂｏｏＨ和５－ＦＵ均能不同程度地引起大肠癌细胞膜脂流动性的减少。且这一效果可因抗癌药５－ＦＵ并用ｔｂｏｏＨ而明显增强，提示细胞膜膜脂流动性的改变是脂质过氧化介导癌细胞功能障碍的重要机制。

In order to investigate the free radical mechanisms of chemotherapy,ef-fects of oxy-radical tbooH and ant icancer drugs on lipid peroxidation(LPO),membranefluidity and DNA content of HR- 8348 cell line were studied.The results showed thatLPO level was increased in early stage of culture with tbooH or some anticancer drugs,meanwhile the DNA stained content had no change,which suggested that the change ofLPO content appeared ahead of that of DNA,However,DNA inhibition in earlystage could be observed if both tbooH and 5-FU were combined.This suggested thatlipoperoxidation of cancer cells induced by oxy-radicals could enhance the effect of anti-cancer cytotoxic drugs. Since cell membrane fluidity can reflect the function of activecells sensitivity,the relation between lipoperoxidation and membrane fluidity were furtherstudied with a fluorecent prob DPH,The results showed that oxy-radical tbooH or anti-cancer drugs 5-FU could decrease the fluidity of cell membrane. This effect could begreater if tbooH and 5- FU were used together. It is suggested that the changes of memb-rane might be an important mechanism involved in the lipoperoxidation-induced damage of cancer cells.