ω-3多不饱和脂肪酸诱导多发性骨髓瘤细胞凋亡及抗增殖机制的研究  

The role and mechanisms of ω-3 polyunsaturated fatty acids in inducing cell apoptosis and anti-proliferation in multiple myeloma

作　　者：赵郁[1] 朱晓婷[1] 王轶楠[1] 

机构地区：[1]河北唐山市人民医院放化疗科,唐山063001

出　　处：《实用肿瘤学杂志》2016年第6期516-522,共7页Practical Oncology Journal

摘　　要：目的探讨ω-3多不饱和脂肪酸(∞-3PUFA)单药或联合糖皮质激素地塞米松(DEX)诱导多发性骨髓瘤(MM)细胞凋亡及抗增殖作用机制。方法采用不同浓度的两种ω-3PUFA单药二十碳五烯酸(EPA)和二十二碳六烯酸(DHA),或与DEX联合处理DEX耐药细胞系MM1R 24 h或48 h后,采用MTI法检测细胞的增殖,流式细胞术检测细胞周期的细胞凋亡,Western blot检测相关凋亡蛋白的表达水平。结果不同浓度EPA或DHA(10、20、50、100μM),及50μM EPA或DHA单药与10μM DEX联合均能够抑制MM1R细胞的增殖,且呈剂量和时间依赖性,联合加药组抑制效果均较单药组明显(P<0.05);不同浓度EPA或DHA作用MM1R细胞48 h后,随着药物浓度增加,G_0/G_1期细胞逐渐增加,S期和G_2期细胞逐渐减少,细胞阻滞在G_0/G_1期,细胞凋亡率逐渐增加。而联合加药组较单药组细胞阻滞和细胞凋亡增加更明显(P<0.05)。凋亡相关蛋白(Cleaved caspase-3、Bax)水平逐渐增加,Pro-caspase-3、BCI-2蛋白水平逐渐减少,且呈剂量依赖性。结论ω-3PUFA能够抑制DEX耐药MM细胞增殖,阻滞细胞周期,诱导细胞凋亡,与DEX联合应用对MM细胞具有协同作用,是一种新型的、有效的逆转MM耐药的治疗药物。Objective To explore the role and mechanisms of ω- 3 polyunsaturated fatty acids（ω-3PUFA）alone or in combination with dexamethasone（DEX） in inducing cell apoptosis and anti-proliferation in multiple myeloma（MM）.Methods DEX resistance MM cell line MM1 R were treated with different concentrations of Eicosapentaenoic acid（EPA） or Docosahexaenoic acid（DHA） alone or in combination with DEX for 24 hrs or 48 hrs.Cell proliferation was detected by MTT.Cell cycle and apoptosis were measured by flow cytometry.The levels of apoptosis related proteins were analyzed by Western blot.Results The proliferation of MM1 R was inhibited by different concentrations（10,20,50,100 μM）of EPA or DHA alone or in combination with 10 μM DEX in a dose- and time- dependent manner.Inhibition effect was significantly higher in combinative groups than in single agent groups（P〈0.05）.The percentage of G0/G1 phase and cell apoptosis rate in MM1 R treated with different concentrations of EPA or DHA alone was increased in a dose- dependent manner,and being significantly higher in combinative groups than in single agent groups（P〈0.05）.The expressive levels of cleaved caspase- 3and Bax were up- regulated,while pro- caspase- 3 and BCL- 2 were down- regulated in a dose- dependent manner.Conclusion ω-3PUFA can inhibit DEX resistant MM cell proliferation,arrest cell cycle and induce cell apoptosis,and has a synergistic anti-resistant effect in combination with DEX,may serve as a new,effective MM drugs.

关 键 词：Ω-3多不饱和脂肪酸 多发性骨髓瘤 地塞米松 细胞耐药 

分 类 号：R733.3[医药卫生—肿瘤]