目的探讨基质细胞衍生因子-1(SDF-1)及其受体 CXCR4在非霍奇金淋巴瘤(NHL)中的表达及其与 NHL 肿瘤浸润的关系。方法采用逆转录聚合酶链反应(RT-PCR)方法检测淋巴结和骨髓基质细胞中 SDF-1α的表达,采用流式细胞术检测淋巴结和骨髓中淋巴瘤细胞 CXCR4受体的表达,并采用 Transwell 微孔隔离室实验检测淋巴瘤细胞在体外向重组人 SDF-1α(rhSDF-1α)的趋化反应。结果侵犯骨髓的 NHL 患者骨髓淋巴瘤细胞和未侵犯骨髓的 NHL 患者骨髓单个核细胞表面CXCR4受体的表达均明显高于正常骨髓(84.10±12.12,72.76±8.73和33.20±7.73,P<0.01),而NHL 患者来源于淋巴结的淋巴瘤细胞 CXCR4的表达亦显著高于反应性增生淋巴结炎患者(101.04+21.89 vs 34.81±9.90,P<0.01)。此外,被淋巴瘤侵犯的骨髓基质细胞高表达 SDF-1α,而未被淋巴瘤侵犯的骨髓及正常骨髓基质细胞表达 SDF-1α低下,二者比较差异有统计学意义(P<0.01);且 NHL 患者淋巴结基质细胞 SDF-1α的表达高于反应性增生淋巴结炎患者(P<0.01)。趋化实验发现三种不同来源的 NHL 患者淋巴结和骨髓的单个核细胞均能向 rhSDF-1α发生趋化反应,且抗 CXCR4单抗可明显抑制上述细胞的迁移。结论 SDF-1/CXCR4生物学轴是介导 NHL 肿瘤侵袭的重要机制,CXCR4在淋巴瘤细胞表面以及 SDF-1在淋巴瘤转移部位的同时高表达与 NHL 瘤细胞的转移和浸润密切相关。
In order to investigate the anti-cancer effects of deguelin and on K562 and K562/ADM cells in vitro and the underlying molecular mechanism and compare the cytotoxicity of deguelin on K562, K562/ADM cells and human peripheral blood mononuclear cells (PBMCs). The effects of de- guelin on cell proliferation were assessed by MTT assay. Apoptosis were detected by AnnexinⅤ/PI double-labeled cytometry. The effects of deguelin on the cell cycle were studied by a propidium io- dide method. Our study showed that deguelin inhibited the proliferation of K562 cell and K562/ADM cell in a time- and dose-dependent manner and had minimal effects on normal human peripheral blood mononuclear cells. The ratio of IC50 value of deguelin of 24 h on K562/ADM cells to K562 cells was only 1.27, which was significantly lower than the ratio of IC50 value of ADM (higher than 20). Deguelin could induce apoptosis of K562 cells and K562/ADM cells. K562 cells were arrested at G2/M phase while K562/ADM cells were arrested at G0/G1 phase. Our results suggested that deguelin was a novel anti-leukemia agents with high efficacy and low toxicity and it is also a promising agent for reversing drug resistance.
