低频超声增强双氢青蒿素诱导前列腺癌PC-3细胞凋亡的生物学效应研究

Biology effect research of dihydroartemisinin induce the apoptosis in PC-3 cell lines of prostate cancer enhanced by low frequency ultrasound

目的研究低频超声能否增强双氢青蒿素(DHA)对前列腺癌PC-3细胞种植瘤的致凋亡作用,并探讨其对DHA诱导前列腺癌PC-3细胞凋亡增敏作用的机理。方法采用前列腺癌PC-3细胞建立裸鼠种植瘤模型,20只实验裸鼠随机分为4组:空白对照组、单纯DHA组、单纯超声组和超声+DHA组,经过13d共计7次药物或加超声干预后,采用免疫组织化学法(SP)检测凋亡相关基因Bcl-2、Bax、VEGF、Caspase-3及CHOP的表达水平。结果观察瘤体外形见空白对照组与单纯超声组肿瘤体积稍大,切开瘤体见内部均有明显液化坏死区域,免疫组织化学结果显示超声+DHA组、单纯DHA组和单纯超声组的Bcl-2及VEGF表达均低于空白对照组,超声+DHA组、DHA组和超声组的Bax、Caspase-3及CHOP表达均高于空白组。结论对正常细胞不致明显损伤的低频超声,可致前列腺癌PC-3种植瘤细胞相关凋亡基因的改变,DHA可单独致PC-3细胞凋亡及相关基因的改变,超声能明显增强DHA诱导前列腺癌PC-3种植瘤细胞凋亡作用。

Objective To study the enhancement effects of the low frequency ultrasound to the apoptosis induced by dihydroartemisinin in the transplantation human prostate cancer PC-3cells in nude mice,and to explore the underlying action mechanism.Methods Prostate cancer PC-3cells were transplanted into 20nude mice to establish the solid tumor mode.These nude mice were randomly divided into 4groups with 5mice in each group：control group,dihydroartemisinin group,ultrasound group and ultrasound ＋ dihydroartemisinin group.After 13days and 7times drug administration,The positive products of Bcl-2,Bax,VEGF,Caspase-3 and CHOP were tested by immunohistochemical method.Results The tumor volume were larger in control group and ultrasound group through observed by tumor contour,and there were liquefication and necrosis region after incised the tumor tissue.Immunohistochemical examination revealed that the positive products of Bcl-2and VEGF were decreased in ultrasound＋DHA group,DHA group and ultrasound group.Immunohistochemical examination revealed that the positive products of Bax、Caspase-3and CHOP were significantly increased in ultrasound＋DHA group,DHA group and ultrasound group.Conclusion The low frequency ultrasound can′t cause obvious damage to the normal cell,which could causing the change of the positive products in transplantation human prostate cancer PC-3cells.The results show that DHA has this action alone,the ultrasound may enhance the apoptosis of PC3cells induced by DHA.