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Article: Effect of cisplatin, topotecan, daunorubicin and hydroxyurea on human mesenchymal stem cells

TitleEffect of cisplatin, topotecan, daunorubicin and hydroxyurea on human mesenchymal stem cells
順鉑、拓撲替康、柔紅霉素和羥基脲對人骨髓間充質干細胞的作用
Authors
KeywordsMesenchymal stem cell (間充質干細胞)
Cisplatin (順鉑)
Topotecan (拓撲替康)
Daunorubicin (柔紅霉素)
Hydroxyurea (羥基脲)
Issue Date2010
Publisher[Beijing Zhonghua Sheng Wu Ji Shu Yan jiu Suo (北京中化生物技術研究所)]. The Journal's web site is located at http://zgsyxyxzz.periodicals.net.cn/
Citation
Journal Of Experimental Hematology, 2010, v. 18 n. 4, p. 991-996 How to Cite?
中國實驗血液學雜誌, 2010, v. 18 n. 4, p. 991-996 How to Cite?
AbstractMesenchymal stem cells (MSC) are important cellular component of the bone marrow microenvironment in supporting hemopoiesis. Li J et al reported previously that MSCs are resistant to chemotherapy commonly used in hematologic malignancies but are relatively sensitive to anti-microtubule agents. However, the response of MSCs to other chemotherapeutic agents commonly used in solid tumour settings remains unknown. This study was purposed to evaluate the acute direct effects of 4 individual chemotherapeutic agents on human MSCs (hMSC), including cisplatin, topotecan, daunorubicin and hydroxyurea. Using an in vitro culture system, the chemosensitivity of hMSC was determined by XTT assay and compared with NB-4 cells and normal peripheral blood mononuclear cells (PBMNC). The recovery of cell numbers following exposure to chemotherapeutic agents and apoptosis induced by chemotherapy in hMSC were evaluated. The results showed that although hMSCs were more resistant to the 4 agents above mentioned than NB-4 cells, they were sensitive to topotecan, cisplatin and daunorubicin than PBMNCs. The IC values of hMSCs for topotecan, cisplatin, hydroxyurea and daunorubicin were 636, 24.8, > 20 and 2.4 times of those of NB-4 cells respectively. The IC values of human PBMNCs for topotecan, cisplatin and daunorubicin were > 27, 1.9 and 1.4 times of those of hMSCs respectively. Reduction of cell number was observed in hMSCs treated with the 4 drugs in clinically relative concentrations. Sustained suppression in hMSCs was observed following 3 days exposure to the 4 agents. It is concluded that the cisplatin, topotecan, daunorubicin and hydroxyurea alone can induce apoptosis of hMSCs and exert persistent suppressive effect on the proliferation of hMSCs even with short term exposure. 我們曾研究一些白血病常用的化療藥物對人間充質干細胞(MSC)的影響,并發現其獨特的耐藥性。本研究評估一些實體瘤常用的化療藥物如順鉑、拓撲替康、柔紅霉素和可長期使用的口服化療藥物如羥基脲等對人MSC的作用。在體外培養系統中,比較人MSC與NB-4細胞系、人外周血單個核細胞(PBMC)對這些單一化療藥物的敏感性。單一化療藥物作用72小時后,繼續將人MSC在正常培養液培養9天,用XTT方法測定細胞增殖恢復情況。AnnexinV/PI染色后,用流式細胞儀檢測上述4種化療藥物誘導的細胞凋亡。結果表明:人MSC對4種化療藥物均較NB-4細胞耐藥,拓撲替康、順鉑、羥基脲和柔紅霉素對人MSC的IC50分別是其對NB-4細胞的IC50的636倍、24.8倍、20倍以上和2.4倍,但人MSC對拓撲替康、順鉑和柔紅霉素較人PBMNC更敏感,拓撲替康、順鉑和柔紅霉素對人PBMNC的IC50分別是其對人MSC的IC50的27倍以上、1.9倍和1.4倍。4種藥物在臨床濃度都明顯抑制人MSC增殖,去除藥物作用后,這種抑制作用持續存在。上述單一藥物臨床濃度作用于人MSC后48-72小時凋亡細胞增加。結論:順鉑、羥基脲、拓撲替康和柔紅霉素單一藥物均可造成人MSC持續損傷,其機制與細胞凋亡有關。
Persistent Identifierhttp://hdl.handle.net/10722/125224
ISSN
2015 SCImago Journal Rankings: 0.134

 

DC FieldValueLanguage
dc.contributor.authorLi, Jen_HK
dc.contributor.authorLaw, HKen_HK
dc.contributor.authorLiu, YLen_HK
dc.contributor.authorChan, GCen_HK
dc.date.accessioned2010-10-31T11:18:31Z-
dc.date.available2010-10-31T11:18:31Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal Of Experimental Hematology, 2010, v. 18 n. 4, p. 991-996en_HK
dc.identifier.citation中國實驗血液學雜誌, 2010, v. 18 n. 4, p. 991-996-
dc.identifier.issn1009-2137en_HK
dc.identifier.urihttp://hdl.handle.net/10722/125224-
dc.description.abstractMesenchymal stem cells (MSC) are important cellular component of the bone marrow microenvironment in supporting hemopoiesis. Li J et al reported previously that MSCs are resistant to chemotherapy commonly used in hematologic malignancies but are relatively sensitive to anti-microtubule agents. However, the response of MSCs to other chemotherapeutic agents commonly used in solid tumour settings remains unknown. This study was purposed to evaluate the acute direct effects of 4 individual chemotherapeutic agents on human MSCs (hMSC), including cisplatin, topotecan, daunorubicin and hydroxyurea. Using an in vitro culture system, the chemosensitivity of hMSC was determined by XTT assay and compared with NB-4 cells and normal peripheral blood mononuclear cells (PBMNC). The recovery of cell numbers following exposure to chemotherapeutic agents and apoptosis induced by chemotherapy in hMSC were evaluated. The results showed that although hMSCs were more resistant to the 4 agents above mentioned than NB-4 cells, they were sensitive to topotecan, cisplatin and daunorubicin than PBMNCs. The IC values of hMSCs for topotecan, cisplatin, hydroxyurea and daunorubicin were 636, 24.8, > 20 and 2.4 times of those of NB-4 cells respectively. The IC values of human PBMNCs for topotecan, cisplatin and daunorubicin were > 27, 1.9 and 1.4 times of those of hMSCs respectively. Reduction of cell number was observed in hMSCs treated with the 4 drugs in clinically relative concentrations. Sustained suppression in hMSCs was observed following 3 days exposure to the 4 agents. It is concluded that the cisplatin, topotecan, daunorubicin and hydroxyurea alone can induce apoptosis of hMSCs and exert persistent suppressive effect on the proliferation of hMSCs even with short term exposure. 我們曾研究一些白血病常用的化療藥物對人間充質干細胞(MSC)的影響,并發現其獨特的耐藥性。本研究評估一些實體瘤常用的化療藥物如順鉑、拓撲替康、柔紅霉素和可長期使用的口服化療藥物如羥基脲等對人MSC的作用。在體外培養系統中,比較人MSC與NB-4細胞系、人外周血單個核細胞(PBMC)對這些單一化療藥物的敏感性。單一化療藥物作用72小時后,繼續將人MSC在正常培養液培養9天,用XTT方法測定細胞增殖恢復情況。AnnexinV/PI染色后,用流式細胞儀檢測上述4種化療藥物誘導的細胞凋亡。結果表明:人MSC對4種化療藥物均較NB-4細胞耐藥,拓撲替康、順鉑、羥基脲和柔紅霉素對人MSC的IC50分別是其對NB-4細胞的IC50的636倍、24.8倍、20倍以上和2.4倍,但人MSC對拓撲替康、順鉑和柔紅霉素較人PBMNC更敏感,拓撲替康、順鉑和柔紅霉素對人PBMNC的IC50分別是其對人MSC的IC50的27倍以上、1.9倍和1.4倍。4種藥物在臨床濃度都明顯抑制人MSC增殖,去除藥物作用后,這種抑制作用持續存在。上述單一藥物臨床濃度作用于人MSC后48-72小時凋亡細胞增加。結論:順鉑、羥基脲、拓撲替康和柔紅霉素單一藥物均可造成人MSC持續損傷,其機制與細胞凋亡有關。en_HK
dc.languagechien_HK
dc.publisher[Beijing Zhonghua Sheng Wu Ji Shu Yan jiu Suo (北京中化生物技術研究所)]. The Journal's web site is located at http://zgsyxyxzz.periodicals.net.cn/en_HK
dc.relation.ispartofJournal of experimental hematologyen_HK
dc.relation.ispartof中國實驗血液學雜誌-
dc.subjectMesenchymal stem cell (間充質干細胞)zh_HK
dc.subjectCisplatin (順鉑)zh_HK
dc.subjectTopotecan (拓撲替康)zh_HK
dc.subjectDaunorubicin (柔紅霉素)zh_HK
dc.subjectHydroxyurea (羥基脲)zh_HK
dc.subject.meshBone Marrow Cells - cytology - drug effects-
dc.subject.meshCisplatin - pharmacology-
dc.subject.meshDaunorubicin - pharmacology-
dc.subject.meshHydroxyurea - pharmacology-
dc.subject.meshMesenchymal Stem Cells - cytology - drug effects-
dc.subject.meshTopotecan - pharmacology-
dc.titleEffect of cisplatin, topotecan, daunorubicin and hydroxyurea on human mesenchymal stem cellsen_HK
dc.title順鉑、拓撲替康、柔紅霉素和羥基脲對人骨髓間充質干細胞的作用-
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1009-2137&volume=18&issue=4&spage=991&epage=996&date=2010&atitle=Effect+of+cisplatin,+topotecan,+daunorubicin+and+hydroxyurea+on+human+mesenchymal+stem+cells-
dc.identifier.emailChan, GC:gcfchan@hkucc.hku.hken_HK
dc.identifier.authorityChan, GC=rp00431en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.pmid20723315-
dc.identifier.scopuseid_2-s2.0-80053363068en_HK
dc.identifier.hkuros179002en_HK
dc.identifier.volume18en_HK
dc.identifier.issue4en_HK
dc.identifier.spage991en_HK
dc.identifier.epage996en_HK
dc.publisher.placeChina (中國)en_HK
dc.identifier.scopusauthoridLi, J=36078695800en_HK
dc.identifier.scopusauthoridLaw, HK=7101939394en_HK
dc.identifier.scopusauthoridLiu, YL=51864176000en_HK
dc.identifier.scopusauthoridChan, GC=16160154400en_HK
dc.customcontrol.immutablecsl 150128-

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