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Multidrug resistance is one of the major causes limiting the efficacy of chemotherapeutic agents used to control osteosarcoma. Multidrug resistance protein 1 (MDR1 or ABCB1) was considered to play a critical role in multidrug resistance. Agents from traditional Chinese medicines (TCMs) have great potential to prevent the onset or delay the progression of the carcinogenic process, and also to enhance the efficacy of mainstream antitumor agents. Herein, we investigated the effect and mechanism of icariin in the human osteosarcoma doxorubicin (DOX)-resistant cell line MG-63/DOX. In this study, icariin exhibited significant effects in sensitization of the resistant cancer cells at a concentration non-toxic to doxorubicin. It also increased the intracellular doxorubicin accumulation and retention in MG-63/DOX cells. In addition, an increase in Rh123 accumulation and a decrease in Rh123 efflux were observed in MG-63/DOX cells treated with icariin, indicating a blockage of the activity of MDR1. Furthermore, icariin enhanced the apoptosis induced by doxorubicin and down-regulated the expression of MDR1. The mechanism involves the inhibition of phosphatidyl inositol 3-kinase (PI3K)/Akt signaling. In conclusion, icariin possesses a reversal effect on multidrug resistance in MG-63/DOX cells through down-regulation of the MDR1 and the PI3K/Akt pathway, and has the potential to be an adjunct to chemotherapy for osteosarcoma.

Titel:	Icariin enhances cytotoxicity of doxorubicin in human multidrug-resistant osteosarcoma cells by inhibition of ABCB1 and down-regulation of the PI3K/Akt pathway.
Autor/in / Beteiligte Person:	Wang, Z ; Yang, L ; Xia, Y ; Guo, C ; Kong, L
Zeitschrift:	Biological & pharmaceutical bulletin, Jg. 38 (2015), Heft 2, S. 277
Veröffentlichung:	Tokyo : Pharmaceutical Society of Japan, c1993-, 2015
Medientyp:	academicJournal
ISSN:	1347-5215 (electronic)
DOI:	10.1248/bpb.b14-00663
Schlagwort:	ATP Binding Cassette Transporter, Subfamily B genetics ATP Binding Cassette Transporter, Subfamily B metabolism ATP Binding Cassette Transporter, Subfamily G, Member 2 ATP-Binding Cassette Transporters genetics ATP-Binding Cassette Transporters metabolism Apoptosis drug effects Cell Line, Tumor Cell Survival drug effects Down-Regulation Humans Multidrug Resistance-Associated Proteins genetics Multidrug Resistance-Associated Proteins metabolism Neoplasm Proteins genetics Neoplasm Proteins metabolism Osteosarcoma drug therapy Osteosarcoma metabolism Phosphatidylinositol 3-Kinase metabolism Proto-Oncogene Proteins c-akt metabolism Antineoplastic Agents pharmacology Doxorubicin pharmacology Drug Resistance, Multiple drug effects Drug Resistance, Neoplasm drug effects Flavonoids pharmacology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Biol Pharm Bull] 2015; Vol. 38 (2), pp. 277-84. MeSH Terms: Antineoplastic Agents / pharmacology ; Doxorubicin / pharmacology ; Drug Resistance, Multiple / drug effects ; Drug Resistance, Neoplasm / drug effects ; Flavonoids / *pharmacology ; ATP Binding Cassette Transporter, Subfamily B / genetics ; ATP Binding Cassette Transporter, Subfamily B / metabolism ; ATP Binding Cassette Transporter, Subfamily G, Member 2 ; ATP-Binding Cassette Transporters / genetics ; ATP-Binding Cassette Transporters / metabolism ; Apoptosis / drug effects ; Cell Line, Tumor ; Cell Survival / drug effects ; Down-Regulation ; Humans ; Multidrug Resistance-Associated Proteins / genetics ; Multidrug Resistance-Associated Proteins / metabolism ; Neoplasm Proteins / genetics ; Neoplasm Proteins / metabolism ; Osteosarcoma / drug therapy ; Osteosarcoma / metabolism ; Phosphatidylinositol 3-Kinase / metabolism ; Proto-Oncogene Proteins c-akt / metabolism Substance Nomenclature: 0 (ABCB1 protein, human) ; 0 (ABCG2 protein, human) ; 0 (ATP Binding Cassette Transporter, Subfamily B) ; 0 (ATP Binding Cassette Transporter, Subfamily G, Member 2) ; 0 (ATP-Binding Cassette Transporters) ; 0 (Antineoplastic Agents) ; 0 (Flavonoids) ; 0 (Multidrug Resistance-Associated Proteins) ; 0 (Neoplasm Proteins) ; 80168379AG (Doxorubicin) ; EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) ; EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) ; VNM47R2QSQ (icariin) ; Y49M64GZ4Q (multidrug resistance-associated protein 1) Entry Date(s): Date Created: 20150310 Date Completed: 20151215 Latest Revision: 20220311 Update Code: 20240513

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Icariin enhances cytotoxicity of doxorubicin in human multidrug-resistant osteosarcoma cells by inhibition of ABCB1 and down-regulation of the PI3K/Akt pathway.