线粒体受体转位蛋白靶向光动力学治疗对结肠癌的作用

Effects of translocation protein-targeted photodynamic therapy in colorectal cancer

目的探讨线粒体受体转位蛋白(TSPO)靶向光动力学治疗(PDT)对结肠癌的作用。方法采用免疫组织化学及Western blotting方法检测氧化偶氮甲烷/葡聚糖硫酸钠(AOM/DSS)诱导的小鼠结肠癌组织及14个结肠癌细胞系中TSPO的表达,使用TSPO靶向光敏剂IR700DX-6T对14个结肠癌细胞系进行PDT。建立小鼠皮下移植瘤模型,进行PDT。结果免疫组织化学结果显示,小鼠结肠癌组织中TSPO的表达明显高于癌旁正常黏膜组织。Western blotting结果证实14个结肠癌细胞系、AOM/DSS诱导的小鼠结肠癌组织及皮下移植瘤组织中的TSPO表达水平明显高于正常结肠黏膜上皮组织。以TSPO为靶向的PDT (TSPO-PDT)可诱导结肠癌细胞死亡,并呈现明显的时间及浓度依赖性(P <0.01)。动物实验证实TSPO-PDT后原发肿瘤和远端肿瘤的生长速度明显小于对照组(P <0.01)。结论 TSPO在结肠癌细胞系和癌组织中均呈高表达,TSPO-PDT可有效抑制结肠癌细胞生长。

Objective To investigate the effect of translocation protein(TSPO)-targeted photodynamic therapy(PDT)targeting the 18 kDA mitochondrial receptor on colorectal cancer cells.Methods The expression of TSPO in azoxymethane/dextran sodium sulfate(AOM/DSS)-induced mouse colorectal cancer(CRC)tissues and 14 CRC cell lines was detected by immunohistochemistry and Western blotting.The 14 CRC cell lines were treated with IR700DX-6T,a TSPO-targeting photosensitizer.A mouse model of a subcutaneous xenograft was established for PDT.Results Immunohistochemistry confirmed that TSPO expression in mouse CRC tissues was significantly higher than that in normal adjacent mucosal tissues.Western blotting analysis confirmed that TSPO expression levels in 14 colorectal cancer cell lines,AOM/DSS-induced mouse CRC tissues,and subcutaneously transplanted tumor tissues were significantly higher than those in normal colonic mucosal epithelial tissues.TSPO-PDT induced CRC cell death and showed significant time and concentration dependence(P<0.01).Animal experiments confirmed that the growth rate of primary and distal tumors after TSPO-PDT treatment was significantly lower than that in the control group(P<0.01).Conclusion TSPO is highly expressed in CRC cells and colon cancer tissues.TSPO-PDT can effec-tively inhibit the growth of CRC.