骨髓基质细胞调控Hedgehog/GLI信号通路抑制HL-60细胞凋亡的研究

孟腾腾; 魏　虹; 管东方

doi:10.19401/j.cnki.1007-3639.2017.07.004

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骨髓基质细胞调控Hedgehog/GLI信号通路抑制HL-60细胞凋亡的研究

更新时间：2025-12-31

- 骨髓基质细胞调控Hedgehog/GLI信号通路抑制HL-60细胞凋亡的研究
- Study on the regulation of Hedgehog/GLI signaling pathway by bone marrow stromal cells to inhibit the apoptosis of HL-60 cells
- 中国癌症杂志 2017年27卷第7期页码：538-544
- 作者机构：
  
  1. 石河子大学医学院组织胚胎学教研室,新疆,石河子,832002
  2. 柘城县人民医院心内科，河南柘城,476200
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2017.07.004
  中图分类号：
- 网络出版：2017-08-16，
  
  纸质出版：2017-08-16
- 稿件说明：
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孟腾腾,，魏　虹,管东方,等. 骨髓基质细胞调控Hedgehog/GLI信号通路抑制HL-60细胞凋亡的研究[J]. 中国癌症杂志, 2017, 27(7): 538-544.

孟腾腾, 魏　虹, 管东方. Study on the regulation of Hedgehog/GLI signaling pathway by bone marrow stromal cells to inhibit the apoptosis of HL-60 cells[J]. China Oncology, 2017, 27(7): 538-544.
孟腾腾,，魏　虹,管东方,等. 骨髓基质细胞调控Hedgehog/GLI信号通路抑制HL-60细胞凋亡的研究[J]. 中国癌症杂志, 2017, 27(7): 538-544. DOI： 10.19401/j.cnki.1007-3639.2017.07.004.

孟腾腾, 魏　虹, 管东方. Study on the regulation of Hedgehog/GLI signaling pathway by bone marrow stromal cells to inhibit the apoptosis of HL-60 cells[J]. China Oncology, 2017, 27(7): 538-544. DOI： 10.19401/j.cnki.1007-3639.2017.07.004.

摘要

背景与目的：骨髓基质细胞(bone marrow stromal cells，BMSC)是造血微环境的核心组成成分。骨髓造血微环境中的BMSC能调节急性髓系白血病(acute myelogenous leukemia，AML)的增殖、存活及耐药。因此，除了直接针对AML的治疗外，阻断白血病与BMSC的相互作用将为白血病的治疗提供新的策略。Hedgehog(Hh)蛋白属于分泌蛋白家族，广泛表达于哺乳动物和非哺乳动物等多个物种中，参与调控多种肿瘤的形成、器官成熟、血管生成、干细胞分化、免疫细胞及胚胎发育。Hh信号可以通过调节肿瘤细胞增殖、分化及免疫来创造适合肿瘤生存的微环境，进而为肿瘤发展和转移创造环境。然而，骨髓造血微环境能否通过Hh信号影响HL-60细胞的存活仍不清楚。该研究旨在探究BMSC诱导的Hh信号对HL-60细胞存活的影响。方法：应用CCK-8试剂盒检测不同实验组间HL-60细胞增殖情况，AnnexinⅤ-FITC/PI双染检测各组HL-60细胞凋亡率，半定量反转录聚合酶链反应(semi-quantitative reverse transcription polymerase chain reaction，SQRT-PCR)等方法检测各实验组Hh信号通路组成成分GLI1基因及凋亡基因BCL-2、BCL-XL的表达情况，免疫荧光法检测GLI1蛋白的表达状况。结果：BMSC对HL-60细胞具有促进增殖和抑制凋亡的作用，以GLI为靶点的Hh信号通路抑制剂GANT6110 μmol/L可以逆转BMSC的这些作用。共培养体系中HL-60细胞GLI1蛋白及mRNA表达上调，抑凋亡基因BCL-2和BCL-XL的mRNA表达上调。结论：BMSC对AML细胞具有保护作用，其机制可能是BMSC激活AML细胞中的Hh信号通路进而上调下游靶基因BCL-2和BCL-XL的表达。

Abstract

Background and purpose: The key component of the hematopoietic microenvironment is bone marrow stromal cells (BMSC). Several studies have provided evidence suggesting that proliferation

survival

and drug resistance of AML can be modulated by BMSC within the bone marrow hematopoietic microenvironment. Therefore

in addition to therapies that directly target acute myelogenous leukemia (AML)

interruption of leukemia cell and BMSC interactions should be considered when designing anti-AML therapeutic strategies. Hedgehog (Hh) protein belongs to a family of secreted proteins

which is widely expressed in mammals and non-mammals species and involved in the regulation of a variety of tumor formation in mature organs

angiogenesis

stem cell differentiation

immune cells

and embryonic development. Hh signaling allows for the modulation of the microenvironment to prepare a tumor-suitable niche by manipulating tumor cell growth

differentiation

and immune regulation

thus creating an enabling environment for progression and metastasis. However

it remains unclear whether the bone marrow hematopoietic microenvironment contributes to the increased survival of HL-60 cells by Hh signaling. Therefore

we studied the influence of bone marrow stromal cell-induced Hh signaling on the survival of HL-60 cells. Methods: CCK-8 kit was used for the detection of HL-60 cell proliferation in different experimental groups. Annexin V-FITC/PI double staining was used to detect the HL-60 cell apoptotic rate. Semiquantitative reverse transcription polymerase chain reaction (SQRT-PCR) was used to detect the experimental group Hh signaling pathway components of GLI1 mRNA and BCL-2

BCL-XL expression. GLI1 apoptotic gene expression levels were measured using immunofluorescence assay. Results: Bone marrow stromal cells promote proliferation and inhibit apoptosis of HL-60 cells

and 10 μmol/L of GANT61 can reverse these effects of bone marrow stromal cells. In co-culture system of HL-60 cells

GLI1 protein and mRNA expression increased and apoptosis inhibiting gene expression of BCL-2 and BCL-XL mRNA were upregulated. Conclusion: Bone marrow stromal cells have a protective effect on acute myeloid leukemia cells. The mechanism may involve activation of the Hh signaling pathway in acute myeloid leukemia cells by bone marrow stromal cells leading to increased expression of downstream target gene BCL-2 and BCL-XL.

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