白藜芦醇通过调控胞内谷胱甘肽氧化还原平衡诱导多发性骨髓瘤U266细胞凋亡

Regulation of the Glutathione Redox Balance Involved in the Apoptosis Induced by Resveratrol in U266 Multiple Myeloma Cells

多发性骨髓瘤是常见于老年人的难治性血液系统肿瘤,对多种常规化疗药物耐药,预后极差。克服耐药性,开发新型化疗药物和治疗策略是极其重要的临床课题。我们的研究发现天然抗肿瘤药物白藜芦醇能有效降低多发性骨髓瘤U266细胞活性并诱导其凋亡。Hoechst33342和TUNEL染色均观察到U266细胞胞核发生了明显的凋亡变化。进一步研究表明,在白藜芦醇诱导U266细胞凋亡的过程中,瘤细胞内谷胱甘肽氧化还原状态发生了明显变化。细胞内过氧化氢含量持续降低,谷胱甘肽总量不变,氧化型谷胱甘肽含量显著增高。瘤细胞内原有的谷胱甘肽氧化还原平衡发生逆转。此外,细胞内超氧化物在白藜芦醇处理48h后呈一过性显著增高,随后逐渐复原。这些研究提示白藜芦醇是通过调控胞内谷胱甘肽氧化还原平衡来发挥其抗多发性骨髓瘤的潜能的。亟待完善的动物实验和临床试验可验证白藜芦醇是否可以作为新型的安全有效的抗肿瘤药物成为一项常规性辅助化疗措施治疗多发性骨髓瘤。

Multiple myeloma is an incurable malignancy of hematological system with a dismal prognosis. It typically occurs in older patients and is resistant to most agents of ordinary chemotherapy. To overcome the chemoresistenco and develop new drugs and novel therapeutic traiegy is very important. Current study investigated that the natural anti--tumor drug, resveratrol, can significantly inhibit the viability of and induce apoptesis in the U266 multiple myeloma cell. Remarkable apoptetic alterations of cellular nucleus in U266 cells were observed by Hoechst33342 stains as well as TUNEL stains methods. Further studies suggested that in the pro- apoptotic procedure, the glutathione redox balance was greatly changed. The intracollular H2O2,significantly decreased. Although the total amount of glutathione was unchanged, that oxidized glutathiane notably increased leaded to the reverse of the inherent glutathione redox balance. Moreover, there was a transient increase in the intracellular superoxide level after 48h of incubation with resveratrol, and then it reduced gradually. Results indicated that resveratrol exhibits its anti-- myeloma potential by reconstructing the glutathiane redox balance. Warranted animal study and pre--clinical trials can further verifiy the ability of resveratrol to manage the multiple myeloma as a novel ordinary adjuvant chemotherapeutic agent which is more safe and effective.