Cheng Yi-Min, Zhu Qi, Jia Pei-Min, Hu Jun-Pei
Department of Hematology, Ninth People Hospital, Shanghai Jiaotong University Medical College, Shanghai 200011, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2007 Dec;15(6):1204-7.
The study was aimed to investigate the possible effects of 8-chloroadenosine 3', 5'-monophosphate (8-Cl-cAMP) on the multiple myeloma cells. The multiple myeloma cell line RPMI8226 was used as in vitro models. The effect on growth inhibition of RPMI8226 cells was evaluated by cell growth and viability curve. DNA fragment was visualized by agarose gel electrophoresis. The amount of apoptosis cells was measured by flow cytometry. Meanwhile Western blot assay were used to detect the change of several key cell cycle regulatory proteins CDK2 and cyclin E in these cells before and after the treatment. The results showed that low dose 8-Cl-cAMP (1-30 micromol/L) inhibited the proliferation and viability of RPMI8226 cells significantly. Agarose gel electrophoresis of DNA revealed the apoptosis characteristic "ladder" pattern. Apoptosis was also confirmed by flow cytometry. In addition, 8-Cl-cAMP was able to inhibit the cell growth through modulating expression of cell cycle regulators CDK2 and cyclin E. It is concluded that 8-cl-cAMP inhibits the proliferation and induce apoptosis of multiple myeloma cells effectively.
本研究旨在探讨8-氯腺苷3',5'-单磷酸(8-Cl-cAMP)对多发性骨髓瘤细胞的可能作用。将多发性骨髓瘤细胞系RPMI8226用作体外模型。通过细胞生长和活力曲线评估对RPMI8226细胞生长抑制的作用。通过琼脂糖凝胶电泳观察DNA片段。采用流式细胞术检测凋亡细胞数量。同时,运用蛋白质免疫印迹法检测处理前后这些细胞中几种关键细胞周期调节蛋白CDK2和细胞周期蛋白E的变化。结果显示,低剂量8-Cl-cAMP(1 - 30微摩尔/升)显著抑制RPMI8226细胞的增殖和活力。DNA的琼脂糖凝胶电泳显示出凋亡特征性的“梯形”图案。流式细胞术也证实了凋亡。此外,8-Cl-cAMP能够通过调节细胞周期调节因子CDK2和细胞周期蛋白E的表达来抑制细胞生长。得出结论:8-Cl-cAMP有效抑制多发性骨髓瘤细胞的增殖并诱导其凋亡。