精氨酸缺乏对硼替佐米治疗多发性骨髓瘤的作用研究

摘要 目的：探讨精氨酸缺乏对硼替佐米(Bortezomib，BTZ) 治疗多发性骨髓瘤细胞的影响。方法：通过CCK8筛选BTZ对骨髓瘤细胞株(H929和RPMI 8226)治疗的最适药物浓度，比较在缺乏和富含精氨酸的两种培养基中的细胞增殖情况；通过使用PI染料标记细胞检测不同试验组细胞周期的分布，以及使用Annexin V/7AAD凋亡试剂盒检测BTZ对不同试验组细胞凋亡的影响。结果：BTZ降低了骨髓瘤细胞的存活率，并通过将细胞周期阻滞于G2/M、S期，抑制骨髓瘤细胞的增殖。缺乏精氨酸使细胞周期阻滞于S期，也抑制了骨髓瘤细胞的增殖。BTZ作用于缺乏精氨酸组的骨髓瘤细胞后，细胞凋亡百分比明显低于富含精氨酸组（H929细胞由约40%降至13.6%，RPMI8226凋亡百分比分别7.13%和19.27%）。结论：缺乏精氨酸和给予BTZ均阻滞细胞周期，抑制骨髓瘤细胞增殖；同时缺乏精氨酸降低了BTZ诱导骨髓瘤细胞的凋亡作用。

Effect of Arginine Deficiency on Myeloma Cell Treated by Bortezomib

ABSTRACT Objective: To investigate the effects of arginine deficiency on multiple myeloma cells treated by bortezomib (BTZ). Methods: In this study, CCK8 was used to screen the optimal drug concentration of BTZ in the treatment of myeloma cell lines (H929 and RPMI 8226). Cell proliferation was compared in the two media lacking and rich in arginine. PI dye-labeled cells were used to detect cell cycle distribution in different experimental groups, and Annexin V/7AAD apoptosis kit was used to detect the effect of BTZ on apoptosis in different experimental groups. Results:: Bortezomib reduced the survival rate of myeloma cells and inhibited the proliferation of myeloma cells by blocking the cell cycle at G2/M and S phases. Lack of arginine blocked the cell cycle in the S phase and also inhibited the proliferation of myeloma cells. After BTZ was applied to the myeloma cells of group lacking the arginine, the percentage of apoptosis was significantly lower than that in the arginine-rich group(13.6% and 40% in H929, 7.13% and 19.27% in RPMI8226). Conclusion: BTZ and the deficiency of arginine can block cell cycle and inhibit the proliferation of myeloma cells, and the lack of arginine reduce the apoptosis of myeloma cells induced by BTZ.