Human myeloma cell apoptosis induced by interferon-α
Human myeloma cell apoptosis induced by interferon-α
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DOI：
10.1046/j.1365-2141.1998.01000.x
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发表时间：
1998-11-01
影响因子：
6.5
通讯作者：
Ueki, A
中科院分区：
文献类型：
--
作者：
Otsuki, T;Yamada, O;Ueki, A
尽管在这十年中已经有关于IFN α在治疗骨髓瘤患者中的临床有效性的报道，但其对人骨髓瘤细胞的生物学效应仍然没有得到澄清。近年来，细胞凋亡被认为是恶性肿瘤细胞程序性死亡的重要机制之一。在诱导细胞凋亡的多种途径中，Fas和Fas配体系统被认为在诱导肿瘤细胞凋亡，特别是在免疫预防中发挥重要作用。在这项研究中，我们研究了由IFN α诱导的骨髓瘤细胞凋亡，使用活的人骨髓瘤细胞系，建立没有任何额外的补充IL-6。此外，还采用逆转录酶-聚合酶链反应（RT-PCR）分析了KMS-12-PE细胞系的凋亡相关基因的mRNA表达水平，该细胞系在IFN α诱导的凋亡方面是五种细胞系中最敏感的。基于结果，确定IFN α以剂量依赖性方式诱导骨髓瘤细胞凋亡，但所检查的细胞系中对IFN α的敏感性不同，并且一个细胞系显示IFN α的生长刺激。此外，IFN α诱导的细胞凋亡似乎不是由Fas/Fas配体途径介导的。最后是IL-6。IFN α诱导KMS-12-PE细胞IL-6 R、IRF 1和IRF 2基因表达上调。因此，这些基因可能在IFN α诱导的细胞凋亡过程中发挥重要作用。
Although there have been reports regarding the clinical effectiveness of IFN alpha in the treatment of myeloma patients during this decade, its biological effects on human myeloma cells have still not been clarified. Recently, apoptosis has been considered as one of the most important mechanisms in the programmed cell death of malignant tumour cells induced by chemotherapeutic agents or cytotoxic immunological defence in malignancy-carrying hosts. Among the several pathways which function to induce apoptosis, Fas and the Fas ligand system have been thought to play an important role in inducing tumour-cell apoptosis, particularly in immunological prevention. In this study we investigated myeloma cell apoptosis induced by IFN alpha using live human myeloma cell lines which were established without any additional supplementation of IL-6. In addition, the mRNA expression levels of apoptosis-related genes employing the reverse transcriptase-polymerase chain reaction (RT-PCR) were also analysed with the KMS-12-PE cell line, which was the most sensitive of the five cell lines in terms of apoptosis induced by IFN alpha. Based on the results, it was determined that IFN alpha induced myeloma cell apoptosis in a dose-dependent manner, but the sensitivity to IFN alpha in the cell lines examined varied and one cell line revealed growth stimulation by IFN alpha. In addition, the apoptosis induced by IFN alpha did not seem to be mediated by the Fas/Fas ligand pathway. Finally, the IL-6. IL-6R, IRF1 and IRF2 genes were up-regulated in KMS-12-PE cells cultured with IFN alpha. Therefore these genes may play an important role during apoptosis induced by IFN alpha.