Experimental study on cAMP analogue combined with arsenic trioxide inducing apoptosis in multiple myeloma cells

杭海芳; 王莹莹; 唐　勇; 庄　衍; 励菁菁; 朱　琦

doi:10.19401/j.cnki.1007-3639.2019.03.002

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Experimental study on cAMP analogue combined with arsenic trioxide inducing apoptosis in multiple myeloma cells

更新时间：2026-01-27

- Experimental study on cAMP analogue combined with arsenic trioxide inducing apoptosis in multiple myeloma cells
- China Oncology Vol. 29, Issue 3, Pages: 166-170(2019)
- 作者机构：
  
  上海交通大学医学院附属第九人民医院血液内科,上海,200011
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2019.03.002
  CLC： R733.3
- Published Online：26 April 2019，
  
  Published：26 April 2019
- 稿件说明：
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杭海芳，王莹莹，唐　勇，庄　衍，励菁菁，朱　琦. 三氧化二砷联合环腺苷酸拟似物诱导骨髓瘤细胞凋亡的实验研究[J]. 中国癌症杂志, 2019, 29(3): 166-170.

杭海芳, 王莹莹, 唐　勇, et al. Experimental study on cAMP analogue combined with arsenic trioxide inducing apoptosis in multiple myeloma cells[J]. China Oncology, 2019, 29(3): 166-170.
杭海芳，王莹莹，唐　勇，庄　衍，励菁菁，朱　琦. 三氧化二砷联合环腺苷酸拟似物诱导骨髓瘤细胞凋亡的实验研究[J]. 中国癌症杂志, 2019, 29(3): 166-170. DOI： 10.19401/j.cnki.1007-3639.2019.03.002.

杭海芳, 王莹莹, 唐　勇, et al. Experimental study on cAMP analogue combined with arsenic trioxide inducing apoptosis in multiple myeloma cells[J]. China Oncology, 2019, 29(3): 166-170. DOI： 10.19401/j.cnki.1007-3639.2019.03.002.

摘要

背景与目的：近年来随着新型药物和免疫疗法的成功应用，多发性骨髓瘤（multiple myeloma，MM）患者的缓解率、缓解深度和无病生存率较以往显著提高，然而仍有相当一部分MM患者属于复发/难治性病例。我们的前期研究发现，环腺苷酸（cyclic adenosine monophosphate，cAMP）拟似物和三氧化二砷（arsenic trioxide，As

）可以抑制MM细胞增殖并诱导其凋亡，成为MM治疗的新途径。该研究进一步探究As

单独和联合环腺苷酸拟似物8-对氯苯硫基环腺苷酸［8-(4-chlorophenylthio) adenosine 3’

5’-cyclic monophosphate，8-CPT-cAMP］对MM细胞的影响及可能作用机制。方法：以不同浓度As

和8-CPT-cAMP单独和联合处理MM细胞系U266细胞，采用细胞计数试剂盒（cell counting kit-8，CCK-8）检测其增殖，应用药物联合指数（combination index，CI）分析两药是否存在协同效应，同时采用流式细胞术检测细胞周期和凋亡率，进一步利用蛋白质印迹法（Western blot）检测细胞凋亡相关蛋白caspase-3和Bcl-2表达的变化。结果：U266细胞经As

和8-CPT-cAMP单独或联合处理72和120 h后，联合用药组细胞增殖抑制率分别为（18.01±0.13）%和（28.01±0.14）%，明显高于单独用药组［As

组为（11.35±0.01）%和（16.01±0.14）%，8-CPTcAMP组为（12.26±0.30）%和（15.43±0.23）%，P均0.05］；但两药联合处理U266细胞的CI值均大于1。联合用药组72和120 h后U266细胞凋亡率分别达到（22.26±0.13）%和（31.03±0.14）%，显著高于单药组［As

组为（10.06±0.01）%和（12.35±0.14）%，8-CPT-cAMP组为（13.26±0.30）%和（18.76±0.23）%，P均0.05］。同时联合用药组U266细胞内caspase-3蛋白剪切活化和Bcl

-2表达下降。结论：As

联合8-CPT-cAMP对MM细胞凋亡诱导效应强于单药，但无协同效应。

Abstract

Background and purpose: With the application of novel agents and immune therapeutic strategies

treatment outcomes of multiple myeloma (MM) patients have dramatically improved including not only rates and depth of response

but also progression-free survival. However

a considerable number of patients become relapsed/refractory cases. Studies revealed that the treatment with cyclic adenosine monophosphate (cAMP) or arsenic trioxide (As

) might be a promising strategy for MM therapy. The present study aimed to explore the possible effects of cAMP analogue 8-(4-chlorophenylthio) adenosine 3’

5’-cyclic monophosphate (8-CPT-cAMP) combined with As

on MM cells and its potential mechanisms. Methods: The MM cell line U266 cells were treated with different concentrations of As

and 8-CPT-cAMP. The proliferation of U266 cells was evaluated through cell counting kit-8 (CCK-8) assay. The synergistic manner of the two agents was determined by calculation of combination index (CI). Meanwhile

flow cytometry was used to analyze the changes of cell cycle distribution and apoptotic rate. Furthermore

Western blot assay was applied to detect expression levels of apoptosis modulator caspase-3 and Bcl-2. Results: After treatment with As

and/or 8-CPT-cAMP for 72 and 120 h

the growth inhibition rates of U266 cells in combination groups reached (18.01±0.13)% and (28.01±0.14)%

which were significantly higher than those in As

or 8-CPT-cAMP alone group ［As

group: (11.35±0.01)% and (16.01±0.14)%; 8-CPT-cAMP group: (12.26±0.30)% and (15.43±0.23)%; P0.05］. The CI value of As

combined with 8-CPT-cAMP was higher than one in U266 cells. The apoptotic rates of U266 cells in combination groups were (22.26±0.13)% and (31.03±

0.14)%

which were significantly higher than those in As

or 8-CPT-cAMP alone group ［As

group: (10.06±0.01)% and (12.35±0.14)%; 8-CPT-cAMP group: (13.26±0.30) % and (18.76±0.23)%; P0.05］. It was also shown that As

combined with 8-CPT-cAMP induced degradation of caspase-3 and down-regulated expression of Bcl-2 in U266 cells. Conclusion: The effect of As

combined with 8-CPT-cAMP on induction of apoptosis in MM cells was stronger than that of single drug

but there was no synergistic effect.

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Related Institution

Department of Hematology/Oncology, Shanghai Second People’s Hospital

Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology

Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine

Department of Stomatology, Affiliated Hospital of Shandong Second Medical University

Shouguang Stomatological Hospital

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