肿瘤坏死因子相关凋亡诱导配体对骨髓瘤裸鼠的抗瘤作用

目的探讨肿瘤坏死因子相关凋亡诱导配体(TRAIL)对接种骨髓瘤细胞裸鼠的抗瘤作用。方法雄性BALB/C裸小鼠共36只,每只小鼠左侧臀部皮下接种9.25×109.L-1骨髓瘤细胞0.2 mL。随机分6组,每组6只:对照组、腹腔高剂量组、腹腔低剂量组、瘤周高剂量组、瘤周低剂量组和腹腔高剂量预防组。给对照组外的各组小鼠给予重组人可溶性TRAIL样品:对照组不给药;高剂量组每只给药剂量为1.5 mg/kg,低剂量组每只给药剂量为0.5 mg/kg。2周后杀鼠测量瘤重、瘤体,常规HE染色观察肿瘤组织形态,并用流式细胞仪检测不同浓度TRAIL作用骨髓瘤细胞后细胞凋亡率和细胞周期的变化。结果瘤周给药组较腹腔给药组效果好,高剂量组较低剂量组效果好,但腹腔高剂量预防组较腹腔高剂量组疗效未有明显优势。流式细胞仪检测结果显示,细胞凋亡率随TRAIL剂量增加而升高。结论 TRAIL能够诱导骨髓瘤细胞凋亡,抑制移植骨髓瘤小鼠瘤体的生长,其疗效与给药途径、剂量相关。

The anti-tumor effects of TNF-related apoptosis-inducing ligand on myeloma in nude mice

Objective To investigate the anti-tumor effects of tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) on mouse with inoculated myeloma.Methods Thirty-six male BALB/C mice were inoculated with myeloma cells(9.25×109·L-1,0.2 mL) under the skin of left hips.These 36 mice were randomly divided into 6 groups: control group(Group A),high dose intrperitoneal injection group(Group B1),low dose intraperitoneal injection group(Group B2),high dose peri-tumor injection group(Group C1),low dose peri-tumor injection group(Group C2),and preventive high dose intraperitoneal injection group(Group D).Human recombinant TRAIL were given peritoneally or peri-tumor with different doses(high dose,1.5 mg/kg;low dose,0.5 mg/kg) in different group,except for Group A.Tumor size and weight were assessed after 2 weeks,and further observed with HE staining.The cell cycle and apoptosis index of SP2/0 cells were analyzed by flow cytometry.Results Significantly higher efficacy was revealed in Group C than that in Group B,while so was in high dose treatment than low dose.However,no significant superiority was observed in Group D than Group B1.Furthermore,TRAIL induced tumor cell apoptosis in a dose-dependent manner.Conclusion TRAIL can induce apoptosis of SP2/0 cells,inhibit the growth of myeloma.The efficacy is correlated with route of administration and dosage.