188Re电脑辐射诱导不同肿瘤细胞凋亡的实验研究

目的通过研究188Re诱导前列腺癌PC-3细胞、乳腺癌ER-75-30细胞、肺癌A549细胞凋亡的作用及相关基因bcl-2和bax在其中的表达,为临床个体化治疗及康复干预提供理论依据。方法人前列腺癌PC-3细胞株、乳腺癌ER-75-30细胞株和非小细胞肺癌A549细胞株经培养后,采用光镜、电镜、流式细胞仪和免疫组化方法研究188Re诱导3种肿瘤细胞凋亡的形态学变化、时间剂量效应关系、细胞周期依赖性以及凋亡相关基因bcl-2和bax在其中的表达情况。结果188Re能诱导肿瘤细胞产生凋亡的形态学变化,并且随着浓度的增大(0～240GBq/L)和时间的延长(6～48h),凋亡率增加,bcl-2表达减弱,bax表达增强,两者比值下降(PC-3由1.07±0.56、1.05±0.48下降至0.23±0.10、0.26±0.10),细胞阻滞于G2/M期。PC-3细胞对188Re的敏感性最高,其次为ER-75-30细胞,A549对188Re的敏感性最低。结论188Re电离辐射能诱导肿瘤细胞凋亡,且呈现时间剂量和周期依赖性;Bcl-2和bax均参与188Re诱导凋亡过程;不同肿瘤细胞对同一种核素的敏感性不同;并为临床个体化治疗和康复干预提供理论依据。

Experimental study on apoptosis of three different tumor cell lines induced by 188Re

Aim By studying apoptosis of human prostate cancer PC-3 cell, breast cancer ER-75-30 cell and lung cancer A549 cell induced by 188Re and detecting expression of bcl-2 and bax genes.We hope to offer theorical basis for clinical individual therapy and recovery interference.Methods Human prostate cancer PC-3 cell, breast cancer ER-75-30 cell and lung cancer A549 cell were cultured in RPMI medium 1640.Light microscope,transmissional electron microscope, flow cytometer and immunohistochemical method were used to observe apoptosis morphological changes of three kinds of tumor cell lines, time and dose effect relationship and to detect expression of bcl-2 and bax.Results 188Re can induce tumor cell producing apoptosis morphological changes.With the rise of radiative dose( 0- 240 GBq/L) and prolongation of culture time( 6- 48 h) , cell apoptosis induced by 188Re increased, expression of bcl-2 protein was enhanced and that of bax protein decreased. The ratio of bcl-2 and bax declined(declining from 1.07± 0.56,1.05± 0.48 to 0.23± 0.10,0.26± 0.10 in PC-3 cell line).Cells were blocked in G2/M period.PC-3 cell was most sensitive and A549 cell was most insensitive to 188Re.Conclusion 188Re can induce apoptosis of tumor cell, which have time and dose and cycle dependence.Both bcl-2 and bax genes play important roles in apoptosis.Diffrent cell line has diffrent sensitivity to 188Re.These can offer theorical basis for clinical individual therapy and recovery interference.