| 周 杰 周荣斌 吴 双 曾 瑞 李建军 梁后杰
△.AG490 上调 BATF2 表达抑制淋巴瘤细胞增殖 *[J].现代生物医学进展英文版,2014,14(6):1025-1028. |
| AG490 上调 BATF2 表达抑制淋巴瘤细胞增殖 * |
| AG490 Suppresses Lymphoma Cell Proliferation by up-regulating BATF2Expression* |
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| DOI： |
| 中文关键词: AG490 STAT 淋巴瘤 BATF2 |
| 英文关键词: AG490 JAK/STAT Lymphoma BATF2 |
| 基金项目:国家自然科学基金项目（ 81172114 ） |
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| 中文摘要: |
| 摘要 目的： AG490 作为 JAK2/STAT3 通路的抑制剂， 在对肿瘤细胞的抑制作用上所展现出的高效低毒性， 使其有望成为临床上
治疗肿瘤的一种可能的药物。 然而， AG490 的抗瘤机制尚未明确。因此， 本文拟对 AG490 抑制淋巴瘤细胞增殖的效应及其作用机
制进行进一步探讨，为 AG490 应用于临床提供实验依据。方法： 用不同剂量的 AG490 处理淋巴瘤细胞 （Namalwa 和 JeKo-1 ） 、 JurkatT 淋巴细胞性白血病细胞和 THP-1 单核细胞性白血病细胞 24 小时， CCK-8 法检测 AG490 (0 μM、 2 μM、 20μM、 50μM、 200μM)对上述细胞的增殖抑制作用， 实时定量 PCR 法检测 BATF2 mRNA 的变化， Western blot 法检测其蛋白水平的变化， 细胞转染
siRNA 法抑制 BATF2 表达后 CCK8 法检测 AG490 对 Namalwa 细胞的增殖抑制效应。结果： AG490 呈剂量依赖性地抑制 Namalwa、 JeKo-1、 Jurkat 细胞的增殖(P<0.05)， 同时上调其 BATF2 mRNA 水平和蛋白水平的表达(P<0.05)。对于无显著抑制作用的
THP-1 细胞， BATF2 的表达亦未见升高(P>0.05)。siRNA 法抑制 BATF2 基因表达后， AG490 对 Namalwa 细胞的增殖抑制效果明
显降低(P<0.05)。 结论： AG490 杀肿瘤细胞的效率与其诱导的 BATF2 的表达呈正相关， 抑制 BATF2 的表达后 AG490 抑制肿瘤细
胞增殖的效率明显降低。因此， AG490 可能是通过上调 BATF2 表达的方式抑制淋巴瘤细胞增殖。这意味着 BATF2 是 AG490 杀
伤淋巴瘤细胞的作用靶点， 可能为新药的开发做出一定的贡献。 |
| 英文摘要: |
| ABSTRACT Objective:The inhibitory effect of AG490, the JAK2/STAT3 pathway inhibitor, on tumor cells with high efficiency
and low toxicity makes it a potential drug that is clinically used to treat tumor . Nevertheless , the mechanism how AG490 suppresses
tumor remains not elusive. Therefore, this paper will investigate the effect and the mechanism of AG490 suppressing lymphoma cell proliferation.Methods: Lymphoma cells (Namalwa and JeKo-1), T-cell leukemia cells (Jurkat) and monocytic leukemia cells (THP-1) were
treated with different doses of AG490(0 μM, 20 μM and 50 μM) for 24h. Cell viability was measured by CCK-8 assay. The mRNA level
of BATF2 was detected by real-time PCR, and the protein level was detected by Western blot. Namalwa cells were transfected with siRNA to inhibit BATF2 expression. Results:Namalwa, JeKo-1 and Jurkat cells were dose-dependently suppressed by AG490 (P<0.05).
Correspondingly, the mRNA and protein expression of BATF2 were significantly up-regulated (P<0.05). However, no significant change
was shown on cell proliferation suppression or BATF2 expression of THP-1 cells (P>0.05). AG490 couldn't inhibit Namalwa cells proliferation when BATF2 was repressed by siRNA.Conclusion: The inhibitory effect of AG490 on lymphoma cells was positively correlated
with the BATF2 expression induction. Moreover, the inhibitory effect was decreased after BATF2 gene was knocked down. Thus, upregulation of BATF2 may be a possible mechanism, by which AG490 inhibits the proliferation of lymphoma cells. These results imply that
BATF2 is the target of AG490 for its anti-lymphoma effect, which might contribute to the development of new drugs. |
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