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目的研究肿瘤坏死因子相关凋亡诱导配体(TRAIL)与化疗药对人骨肉瘤的联合作用及其受体(TRAILR)在人骨肉瘤中的表达间的关系。方法应用细胞计数、AO/EB染色、流式细胞术等方法比较检测阿霉素、顺铂、甲氨喋呤、紫杉醇单独作用和与TRAIL联合作用于MG-63及骨肉瘤组织的细胞毒效应;应用原位杂交、WesternBlot方法检测人骨肉瘤细胞系MG-63及新鲜骨肉瘤组织用药前后TRAILR的表达。结果阿霉素、顺铂和紫杉醇增强死亡受体的表达,且与TRAIL联合作用诱导人骨肉瘤细胞凋亡的效率显著强于单用。结论阿霉素、顺铂、紫杉醇通过上调DR4、DR5表达逆转人骨肉瘤对TRAIL的耐受。
Objective To study the combined effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and chemotherapeutics on human osteosarcoma and the expression of its receptor (TRAILR) in human osteosarcoma. Methods Cytotoxic effects of adriamycin, cisplatin, methotrexate, paclitaxel alone and in combination with TRAIL on MG-63 and osteosarcoma were detected by cell counting, AO / EB staining and flow cytometry The expression of TRAILR in human osteosarcoma cell line MG-63 and fresh osteosarcoma tissue was detected by in situ hybridization and Western Blot. Results Adriamycin, cisplatin and paclitaxel enhanced the expression of death receptor, and combined with TRAIL induced apoptosis of human osteosarcoma cells was significantly more effective than single use. Conclusion Adriamycin, cisplatin and paclitaxel can reverse the tolerance of human osteosarcoma to TRAIL by up-regulating DR4 and DR5 expression.