氯喹增敏地塞米松或辐射对多发性骨髓瘤细胞的杀伤作用

付慧; 陶玉龙; 倪敏; 李冬洁; 沈甫明

doi:10.3969/j.issn.1006-0111.2016.03.005

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

x 关闭永久关闭

应中央军委要求，2022年9月起，《药学实践杂志》将更名为《药学实践与服务》，双月刊，正文96页；2023年1月起，拟出版月刊，正文64页，数据库收录情况与原《药学实践杂志》相同。欢迎作者踊跃投稿！

氯喹增敏地塞米松或辐射对多发性骨髓瘤细胞的杀伤作用

付慧, 陶玉龙, 倪敏, 李冬洁, 沈甫明

文章导航 > 药学实践与服务 > 2016 > 34(3): 210-214

付慧, 陶玉龙, 倪敏, 李冬洁, 沈甫明. 氯喹增敏地塞米松或辐射对多发性骨髓瘤细胞的杀伤作用[J]. 药学实践与服务, 2016, 34(3): 210-214. doi: 10.3969/j.issn.1006-0111.2016.03.005

引用本文:

FU Hui, TAO Yulong, NI Min, LI Dongjie, SHEN Fuming. Sensitized cytotoxic effects of dexamethasone or radiation on multiple myeloma cells by chloroquine[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(3): 210-214. doi: 10.3969/j.issn.1006-0111.2016.03.005

Citation:

FU Hui, TAO Yulong, NI Min, LI Dongjie, SHEN Fuming. Sensitized cytotoxic effects of dexamethasone or radiation on multiple myeloma cells by chloroquine[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(3): 210-214. doi: 10.3969/j.issn.1006-0111.2016.03.005

氯喹增敏地塞米松或辐射对多发性骨髓瘤细胞的杀伤作用

doi: 10.3969/j.issn.1006-0111.2016.03.005

1.
第二军医大学药学院药理学教研室, 上海 200433
2.
第二军医大学附属长征医院药学部, 上海 200003
3.
同济大学附属上海第十人民医院药学部, 上海 200072
4.
第二军医大学药学院药理学教研室, 上海 200433;同济大学附属上海第十人民医院药学部, 上海 200072

基金项目: 国家重大新药创制(2011ZXJ09201-012)

Sensitized cytotoxic effects of dexamethasone or radiation on multiple myeloma cells by chloroquine

1.
Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
2.
Department of Pharmacy, Changzheng Hospital Affiliated to Second Military Medical University, Shanghai 200433, China
3.
Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China
4.
Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China;Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China

摘要: 目的研究氯喹(chloroquine, CQ),及CQ是否增敏化疗药物地塞米松(dexamethasone, DEX)或辐射对多发性骨髓瘤细胞株U266细胞的杀伤作用,并探讨其可能机制。方法用细胞活性检测试剂盒(cell counting kit-8, cck8)检测CQ单药,以及CQ联用DEX对U266细胞增殖的影响,运用中效原理软件评估两药相互作用;cck8及流式细胞术分别检测CQ处理条件下辐射对U266细胞增殖和凋亡作用的改变;Western blot检测CQ合用DEX,以及CQ联合辐射对U266细胞内B细胞淋巴瘤-2(B-cellymphoma-2, Bcl-2)蛋白表达变化。结果 CQ及DEX对U266细胞的增殖抑制作用呈浓度依赖性,且CQ(3.9 μmol/L)能够增强DEX(125 μmol/L)对U266细胞的杀伤作用,并增加DEX降低细胞内抗凋亡蛋白Bcl-2的表达水平;不同辐射剂量(5~25 Gy)对U266细胞的生长抑制作用并无差异;CQ(1.0 μmol/L)可以增加辐射对U266细胞的敏感性,诱导细胞凋亡。结论 CQ能够增敏DEX或辐射对U266细胞的杀伤作用,CQ增敏DEX的作用机制可能与抑制Bcl-2蛋白表达相关。
- 氯喹 /
- 地塞米松 /
- 辐射 /
- 多发性骨髓瘤细胞株U266细胞 /
- 增敏
Abstract: Objective To investigate the role and possible mechanism of combination use of chloroquine (CQ) with either dexamethasone (DEX) or radiation on multiple myeloma (MM) cell line U266. Methods Cell viability of U266 treated with CQ alone, or CQ combined with either DEX or radiation was measured by cell counting kit-8(cck8). CalcuSyn method was used to assess effect of drugs interaction. Cell viability and apoptosis of U266 pre-treated with CQ were also measured by cck8 and flow cytometry after radiation. Expression of B-cellymphoma-2(Bcl-2) in U266 cells treated by CQ combined with DEX or radiation was determined by Western blot analysis. Results Either CQ or DEX displayed a dose dependent cell proliferation inhibitory effect on U266 cells. Cytotoxic effect of DEX (125 μmol/L) on U266 cells was enhanced and expression of Bcl-2 protein in U266 cells was decreased by combining with CQ (3.9 μmol/L). U266 cells were sensitized to radiation and cell death was induced by CQ (1.0 μmol/L). Conclusion CQ could sensitize cytotoxic effect of DEX or radiation on U266 cells, and the former was possibly related to down-regulation of Bcl-2 protein.
- chloroquine /
- dexamethasone /
- radiation /
- multiple myeloma cell line U266 /
- sensitization

[1]	Feng W, Fu Y, Zhang Y, et al. Establishment of stable multiple myeloma cell line with overexpressed PDCD5 and its proapoptosis mechanism[J]. Int J Clin Exp Pathol, 2015,8:10635-10643.
[2]	Dong H, Carlton ME, Lerner A, et al. Effect of cAMP signaling on expression of glucocorticoid receptor, Bim and Bad in glucocorticoid-sensitive and resistant leukemic and multiple myeloma cells[J]. Front Pharmacol, 2015,6:230.
[3]	Solomon VR, Lee H. Chloroquine and its analogs:a new promise of an old drug for effective and safe cancer therapies[J]. Eur J Pharmacol, 2009,625:220-233.
[4]	Fukuda T, Oda K, Wada-Hiraike O, et al. The anti-malarial chloroquine suppresses proliferation and overcomes cisplatin resistance of endometrial cancer cells via autophagy inhibition[J]. Gynecol Oncol, 2015,137:538-545.
[5]	Hu T, Li P, Luo Z, et al. Chloroquine inhibits hepatocellular carcinoma cell growth in vitro and in vivo[J]. Oncol Rep, 2015,35:43-49.
[6]	Tang MC, Wu MY, Hwang MH, et al. Chloroquine enhances gefitinib cytotoxicity in gefitinib-resistant nonsmall cell lung cancer cells[J]. PLoS One, 2015,10:e0119135.
[7]	Han MW, Lee JC, Choi JY, et al. Autophagy inhibition can overcome radioresistance in breast cancer cells through suppression of TAK1 activation[J]. Anticancer Res, 2014,34:1449-1455.
[8]	Ghafouri-Fard S, Seifi-Alan M, Shamsi R, et al. Immunotherapy in multiple myeloma using cancer-testis antigens[J]. Iran J Cancer Prev, 2015,8:e3755.
[9]	Lambert KE, Huang H, Mythreye K, et al. The type Ⅲ transforming growth factor-beta receptor inhibits proliferation, migration, and adhesion in human myeloma cells[J]. Mol Biol Cell, 2011,22:1463-1472.
[10]	刘竞,李昕,桂嵘,等. 程序化细胞死亡分子-5蛋白对地塞米松诱导的多发性骨髓瘤细胞凋亡的影响[J]. 中国老年学杂志, 2010,30:1972-1974.
[11]	Lee SW, Kim HK, Lee NH, et al. The synergistic effect of combination temozolomide and chloroquine treatment is dependent on autophagy formation and p53 status in glioma cells[J]. Cancer Lett, 2015,360:195-204.
[12]	Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method[J]. Cancer Res, 2010,70:440-446.
[13]	袁晓丽,李涛,黄建鸣,等. 氯喹对食管癌细胞系放射增敏的实验研究[J]. 中国放射医学与防护杂志, 2014,34:823-826.
[14]	MS Ola MN, Ahsan H. Role of Bcl-2 family proteins and caspases in the regulation of apoptosis[J]. Mol Cell Biochem, 2011,351:41-58.
[15]	Niizuma K, Yoshioka H, Chen H, et al. Mitochondrial and apoptotic neuronal death signaling pathways in cerebral ischemia[J]. Biochim Biophys Acta, 2010,1802:92-99.

[1]	黄韵, 张正银, 金英, 郑怡菁, 李铁军, 孙莉莉. 耐碳青霉烯类肺炎克雷伯菌及大肠埃希菌临床分离株耐药性及耐药基因分析 . 药学实践与服务, 2024, 42(10): 439-444. doi: 10.12206/j.issn.2097-2024.202309059
[2]	刘丽艳, 余小翠, 孙传铎. 纳武利尤单抗治疗非小细胞肺癌有效性及安全性的Meta分析 . 药学实践与服务, 2024, 42(10): 451-456. doi: 10.12206/j.issn.2097-2024.202310044
[3]	宋雨桐, 夏德润, 顾珩, 唐少文, 易洪刚, 沃红梅. 帕博利珠单抗与铂类化疗方案在晚期非小细胞肺癌一线治疗中的药物经济学评价 . 药学实践与服务, 2024, 42(8): 334-340. doi: 10.12206/j.issn.2097-2024.202303023
[4]	冯志惠, 邓仪卿, 叶冰, 安培, 张宏, 张海军. 雀梅藤石油醚提取物诱导三阴性乳腺癌细胞凋亡的实验研究 . 药学实践与服务, 2024, 42(6): 253-259. doi: 10.12206/j.issn.2097-2024.202311055
[5]	修建平, 杨朝爱, 刘禧澳, 潘乾禹, 韦广旭, 王卫星. 全反式维甲酸对肝星状细胞活化及氧化应激的作用和机制探索 . 药学实践与服务, 2024, 42(7): 291-296. doi: 10.12206/j.issn.2097-2024.202312054
[6]	姜涛, 徐卫凡, 蒋益萍, 夏天爽, 辛海量. 巴戟天丸组方对Aβ损伤成骨细胞的作用及基于网络药理学的机制研究 . 药学实践与服务, 2024, 42(7): 285-290, 296. doi: 10.12206/j.issn.2097-2024.202305011
[7]	杨媛媛, 安晓强, 许佳捷, 江键, 梁媛媛. 正极性驻极体联合5-氟尿嘧啶对瘢痕成纤维细胞生长抑制的协同作用 . 药学实践与服务, 2024, 42(6): 244-247. doi: 10.12206/j.issn.2097-2024.202310027
[8]	迟文雅, 袁艳, 李伟林, 吴茼妤, 俞媛. 负载骨髓间充质干细胞/白藜芦醇脂质体的水凝胶支架用于创伤性脑损伤治疗 . 药学实践与服务, 2024, 42(): 1-8. doi: 10.12206/j.issn.2097-2024.202406034

点击查看大图

计量

文章访问数: 3143
HTML全文浏览量: 311
PDF下载量: 14
被引次数: 0

氯喹增敏地塞米松或辐射对多发性骨髓瘤细胞的杀伤作用

doi: 10.3969/j.issn.1006-0111.2016.03.005

1. 第二军医大学药学院药理学教研室, 上海 200433

2. 第二军医大学附属长征医院药学部, 上海 200003

3. 同济大学附属上海第十人民医院药学部, 上海 200072

4. 第二军医大学药学院药理学教研室, 上海 200433;同济大学附属上海第十人民医院药学部, 上海 200072

基金项目: 国家重大新药创制(2011ZXJ09201-012)

收稿日期: 2016-03-09
修回日期: 2016-04-14

关键词:

氯喹 /

地塞米松 /

辐射 /

多发性骨髓瘤细胞株U266细胞 /

增敏

摘要: 目的研究氯喹(chloroquine, CQ),及CQ是否增敏化疗药物地塞米松(dexamethasone, DEX)或辐射对多发性骨髓瘤细胞株U266细胞的杀伤作用,并探讨其可能机制。方法用细胞活性检测试剂盒(cell counting kit-8, cck8)检测CQ单药,以及CQ联用DEX对U266细胞增殖的影响,运用中效原理软件评估两药相互作用;cck8及流式细胞术分别检测CQ处理条件下辐射对U266细胞增殖和凋亡作用的改变;Western blot检测CQ合用DEX,以及CQ联合辐射对U266细胞内B细胞淋巴瘤-2(B-cellymphoma-2, Bcl-2)蛋白表达变化。结果 CQ及DEX对U266细胞的增殖抑制作用呈浓度依赖性,且CQ(3.9 μmol/L)能够增强DEX(125 μmol/L)对U266细胞的杀伤作用,并增加DEX降低细胞内抗凋亡蛋白Bcl-2的表达水平;不同辐射剂量(5~25 Gy)对U266细胞的生长抑制作用并无差异;CQ(1.0 μmol/L)可以增加辐射对U266细胞的敏感性,诱导细胞凋亡。结论 CQ能够增敏DEX或辐射对U266细胞的杀伤作用,CQ增敏DEX的作用机制可能与抑制Bcl-2蛋白表达相关。

English Abstract

Sensitized cytotoxic effects of dexamethasone or radiation on multiple myeloma cells by chloroquine

1. Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China

2. Department of Pharmacy, Changzheng Hospital Affiliated to Second Military Medical University, Shanghai 200433, China

3. Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China

4. Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China;Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China

Received Date: 2016-03-09
Rev Recd Date: 2016-04-14

Keywords:

Abstract: Objective To investigate the role and possible mechanism of combination use of chloroquine (CQ) with either dexamethasone (DEX) or radiation on multiple myeloma (MM) cell line U266. Methods Cell viability of U266 treated with CQ alone, or CQ combined with either DEX or radiation was measured by cell counting kit-8(cck8). CalcuSyn method was used to assess effect of drugs interaction. Cell viability and apoptosis of U266 pre-treated with CQ were also measured by cck8 and flow cytometry after radiation. Expression of B-cellymphoma-2(Bcl-2) in U266 cells treated by CQ combined with DEX or radiation was determined by Western blot analysis. Results Either CQ or DEX displayed a dose dependent cell proliferation inhibitory effect on U266 cells. Cytotoxic effect of DEX (125 μmol/L) on U266 cells was enhanced and expression of Bcl-2 protein in U266 cells was decreased by combining with CQ (3.9 μmol/L). U266 cells were sensitized to radiation and cell death was induced by CQ (1.0 μmol/L). Conclusion CQ could sensitize cytotoxic effect of DEX or radiation on U266 cells, and the former was possibly related to down-regulation of Bcl-2 protein.