Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo, PO Box 1112, Blindern, N-0317 Oslo, Norway.
Cancer Lett. 2013 Jul 28;335(2):323-31. doi: 10.1016/j.canlet.2013.02.042. Epub 2013 Feb 26.
There is a continuous search for new therapeutic targets for treatment of multiple myeloma (MM). Here we investigated the mechanisms involved in cAMP-induced apoptosis of human MM cells. cAMP-increasing agents rapidly inhibited activation of JAK1 and its substrate STAT3. In line with STAT3 being a regulator of Mcl-1 transcription, the expression of this pro-survival factor was rapidly and selectively reduced. Notably, exogenous interleukin-6 neither prevented the inhibition of JAK1/STAT3 nor the death of MM cells induced by cAMP. Our results suggest that cAMP-mediated killing of MM cells involves inhibition of the JAK/STAT pathway, making the cAMP-pathway a promising target for treatment of MM.
目前，人们一直在寻找新的治疗靶点，以用于多发性骨髓瘤（MM）的治疗。在此，我们研究了 cAMP 诱导人 MM 细胞凋亡所涉及的机制。cAMP 增加剂可迅速抑制 JAK1 及其底物 STAT3 的激活。与 STAT3 作为 Mcl-1 转录的调节剂一致，这种抗凋亡因子的表达迅速且选择性地降低。值得注意的是，外源性白细胞介素 6 既不能防止 cAMP 诱导的 JAK1/STAT3 抑制，也不能阻止 MM 细胞的死亡。我们的结果表明，cAMP 介导的 MM 细胞杀伤涉及 JAK/STAT 通路的抑制，这使得 cAMP 通路成为治疗 MM 的一个有前途的靶点。
