title: Cross-drug resistance to sunitinib induced by doxorubicin in endothelial cells.
abstract: Multiple drug resistance remains an unsolved problem in cancer therapy. A previous study has demonstrated that the chemotherapeutic drug doxorubicin (Dox) induced upregulation of P-glycoprotein in endothelial cells, resulting in a 20-fold increase in drug resistance and reduced efficiency of doxorubicin treatment in a mouse tumor model. In the present study, the cross-resistance and sensitivity of HMECd1 and HMECd2 established cell lines to anti-angiogenic drugs, particularly sunitinib, was explored. The results revealed that Dox treatment induced a significant increase in the breast cancer resistance protein (ABCG2) gene transcription and protein expression. This increase gave rise to a 4- to 5-fold increase in the half maximal inhibitory concentration of the HMECd1 and HMECd2 cells in response to sunitinib treatmentin vitro. Functionally, the role of ABCG2 in the resistance to sunitinib was confirmed by the use of the ABCG2 inhibitors fumitremorgin C and diethylstilbestrol, which blocked cell resistance. The present study indicates that endothelial cells exhibit cross-resistance between cytotoxic drugs and anti-angiogenic drugs. This suggests that multiple drug resistance induced by chemotherapy in endothelial cells may affect the efficiency of anti-angiogenic drugs.
authors: Department of Oncology, People's Hospital of Guizhou Province, Guiyang, Guizhou 550000, P.R. China.
authors: Limin
authors: L
authors: Huang
authors: Department of Surgery, Affiliated Hospital of Guiyang Medical University, Guiyang, Guizhou 550004, P.R. China.
authors: Chaoquan
authors: C
authors: Hu
authors: French Institute of Health and Medical Research, UMR-S 1165, University Institute of Hematology, Saint Louis Hospital, Paris 75010, France.
authors: Mélanie
authors: M
authors: DI Benedetto
authors: Laboratory of MERCI (EA 3829), Faculty of Medicine and Pharmacy, University of Rouen, Rouen 76183, France.
authors: Rémi
authors: R
authors: Varin
authors: Department of Surgery, Affiliated Hospital of Guiyang Medical University, Guiyang, Guizhou 550004, P.R. China ; French Institute of Health and Medical Research, UMR-S 1165, University Institute of Hematology, Saint Louis Hospital, Paris 75010, France.
authors: Jielin
authors: J
authors: Liu
authors: French Institute of Health and Medical Research, UMR-S 1165, University Institute of Hematology, Saint Louis Hospital, Paris 75010, France ; School of Medicine and Pharmaceutics, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors: Jian
authors: J
authors: Jin
authors: French Institute of Health and Medical Research, UMR-S 1165, University Institute of Hematology, Saint Louis Hospital, Paris 75010, France.
authors: Li
authors: L
authors: Wang
authors: Laboratory of MERCI (EA 3829), Faculty of Medicine and Pharmacy, University of Rouen, Rouen 76183, France.
authors: Jean-Pierre
authors: JP
authors: Vannier
authors: French Institute of Health and Medical Research, UMR-S 1165, University Institute of Hematology, Saint Louis Hospital, Paris 75010, France ; Laboratory of Pathology, Paris Diderot University, Sorbonne Paris Cité, UMR-S 1165, France ; Saint-Louis Hospital, Laboratory of Pathology, Paris 75010, France.
authors: Anne
authors: A
authors: Janin
authors: French Institute of Health and Medical Research, UMR-S 1165, University Institute of Hematology, Saint Louis Hospital, Paris 75010, France ; Laboratory of Pathology, Paris Diderot University, Sorbonne Paris Cité, UMR-S 1165, France.
authors: He
authors: H
authors: Lu
authors: Laboratory of MERCI (EA 3829), Faculty of Medicine and Pharmacy, University of Rouen, Rouen 76183, France.
authors: Hong
authors: H
authors: Li
keywords: ABC family; cancer therapy; drug resistance; endothelial cells; sunitinib