摘要
目的 了解多发性骨髓瘤(MM)患者骨髓单个核细胞(BMMNC)及骨髓瘤细胞系(KM3细胞)中4种TRAIL受体的表达情况,探讨TRAIL的选择性杀瘤机制及化疗药物对TRAIL受体的影响。方法 应用半定量RT PCR和流式细胞术检测23例MM患者、15名正常对照者BMMNC和KM3细胞中4种TRAIL受体的表达,并比较了12例MM患者化疗前后BMMNC及KM3细胞与阿霉素共孵育前后4种TRAIL受体表达的变化。结果 MM患者BMMNC死亡受体DR4、DR5的表达均高于正常对照组(P<0. 05),DR5的表达高于DR4(P<0. 05);诱捕受体DcR1、DcR2在MM组中的表达明显低于正常对照组(P<0. 05);KM3细胞死亡受体DR4、DR5强表达,未检测到诱捕受体DcR1、DcR2的表达; MM患者化疗后BMMNC及KM3细胞与阿霉素共孵育后DR5的表达均上调(P<0. 05)。结论 死亡受体DR4、DR5和诱捕受体DcR1、DcR2在MM患者BMMNC和正常人BMMNC中表达有差异,这可能是TRAIL可以选择性杀死MM细胞而对正常细胞无毒性作用的机制之一; MM患者化疗后BMMNC及KM3细胞与阿霉素共孵育后死亡受体DR5表达上调,提示化疗药物可能通过上调死亡受体DR5的表达而促使细胞凋亡。
Objective To study the differential expression of four TRAIL receptors on bone marrow mononuclear cells (BMMNC) from multiple myeloma (MM) patients and myeloma cell line KM3 cells, to compare their altered expressions after chemotherapy and to explore the mechanisms by which TRAIL selectively kills tumor cells. Methods Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry were used to investigate the expression of four TRAIL receptors on BMMNCs in 23 MM patients, KM3 cells and 15 controls, and the changes of their expression pattern after chemotherapy and after incubation of KM3 cells with sub-clinical concentration of doxorubicin. Results DR4 and DR5 were highly expressed on KM3 cells with no expression of DcR1 and DcR2. Expressions of DR4 and DR5 on BMMNCs from MM patients were higher and expression of DcR1 and DcR2 were lower than that of controls( P<0.05 ). The expression of DR5 on MM and KM3 cells was up-regulated after chemotherapy and exposure to doxorubicin (P<0. 05). Conclusions The expressions of four TRAIL receptors on myeloma cells and normal controls were different, which might account for the selective killing effect of TRAIL on MM cells. Up-regulated DR5 on KM3 cells after incubating with doxorubicin and after chemotherapy suggests the cytotoxic agents might enhance the apopotosis of MM cells.
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2005年第4期214-217,共4页
Chinese Journal of Hematology
