Abstract
目的探讨CXCR4/STAT3在骨髓基质细胞介导的急性髓系白血病(AML)细胞耐药中的作用。方法将AML细胞系U937、KG1a和原代AML细胞与健康供者来源的骨髓基质细胞共培养，单独培养的细胞作为对照组。通过膜联蛋白Ⅴ (Annexin Ⅴ)／碘化丙锭(PI)双染色法比较共培养前后AML细胞对米托蒽醌诱导的凋亡的差异，并通过流式细胞术、实时定量PCR及Western blot法检测共培养前后AML细胞CXCR4、磷酸化STAT3(p-STAT3)蛋白的表达；在培养体系中加入STAT3的特异性抑制剂Cucurbitacin Ⅰ或CXCR4拮抗剂AMD3100，检测AML细胞对米托蒽醌诱导的凋亡的变化，并观察AMD3100对p-STAT3表达的影响。结果U937、KG1a细胞与骨髓基质细胞共培养后，对米托蒽醌诱导的凋亡率均低于对照组[U937：(20.08±1.53)%对(45.33±1.03)%，P=0.004; KG1a：(25.60 ± 1.82)%对(40.33±3.29)%，P=0.003]。共培养后，Western blot方法检测发现AML细胞p-STAT3的蛋白表达明显上调，流式细胞术和Western blot检测结果显示CXCR4蛋白表达显著上调，实时定量PCR检测显示CXCR4 mRNA水平明显增高；STAT3的特异性抑制剂Cucurbitacin Ⅰ或CXCR4拮抗剂AMD3100加入共培养体系后，原代AML细胞对米托蒽醌诱导的凋亡率较对照组显著升高，差异均有统计学意义(P值均<0.05)，且加入AMD3100后AML细胞p-STAT3蛋白的表达显著下降。结论AML细胞与骨髓基质细胞共培养可导致p-STAT3、CXCR4蛋白表达的上调，从而导致AML细胞对化疗药物的耐药；针对STAT3、CXCR4的联合靶向治疗可能为AML的治疗提供新思路。
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