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P-glycoprotein breast cancer mdr

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https://www.readbyqxmd.com/read/28052008/targeting-p-glycoprotein-function-p53-and-energy-metabolism-combination-of-metformin-and-2-deoxyglucose-reverses-the-multidrug-resistance-of-mcf-7-dox-cells-to-doxorubicin
#1
Chaojun Xue, Changyuan Wang, Yaoting Sun, Qiang Meng, Zhihao Liu, Xiaokui Huo, Pengyuan Sun, Huijun Sun, Xiaodong Ma, Xiaochi Ma, Jinyong Peng, Kexin Liu
Multidrug resistance(MDR) is a major obstacle to efficiency of breast cancer chemotherapy. We investigated whether combination of metformin and 2-deoxyglucose reverses MDR of MCF-7/Dox cells and tried to elucidate the possible mechanisms. The combination of metformin and 2-deoxyglucose selectively enhanced cytotoxicity of doxorubicin against MCF-7/Dox cells. Combination of the two drugs resumed p53 function via inhibiting overexpression of murine doubleminute 2(MDM2) and murine doubleminute 4(MDM4) leading to G2/M arrest and apoptosis in MCF-7/Dox cells...
December 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/28005280/abcg2-bcrp-specific-and-nonspecific-modulators
#2
REVIEW
Diana Peña-Solórzano, Simone Alexandra Stark, Burkhard König, Cesar Augusto Sierra, Cristian Ochoa-Puentes
Multidrug resistance (MDR) in cancer cells is the development of resistance to a variety of structurally and functionally nonrelated anticancer drugs. This phenomenon has become a major obstacle to cancer chemotherapy seriously affecting the clinical outcome. MDR is associated with increased drug efflux from cells mediated by an energy-dependent mechanism involving the ATP-binding cassette (ABC) transporters, mainly P-glycoprotein (ABCB1), the MDR-associated protein-1 (ABCC1), and the breast cancer resistance protein (ABCG2)...
December 22, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28000875/fulvestrant-reverses-doxorubicin-resistance-in-multidrug-resistant-breast-cell-lines-independent-of-estrogen-receptor-expression
#3
Yuan Huang, Donghai Jiang, Meihua Sui, Xiaojia Wang, Weimin Fan
Drug resistance, a major obstacle to successful cancer chemotherapy, frequently occurs in recurrent or metastatic breast cancer and results in poor clinical response. Fulvestrant is a new type of selective estrogen receptor (ER) downregulator and a promising endocrine therapy for breast cancer. In this study, we evaluated the combination treatment of fulvestrant and doxorubicin in ER-negative multidrug-resistant (MDR) breast cancer cell lines Bads‑200 and Bats‑72. Fulvestrant potentiated doxorubicin-induced cytotoxicity, apoptosis and G2/M arrest with upregulation of cyclin B1...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/27956367/systematic-evaluation-of-multifunctional-paclitaxel-loaded-polymeric-mixed-micelles-as-a-potential-anticancer-remedy-to-overcome-multidrug-resistance
#4
Jiulong Zhang, Xiufeng Zhao, Qing Chen, Xiaoyi Yin, Xiu Xin, Kexin Li, Mingxi Qiao, Haiyang Hu, Dawei Chen, Xiuli Zhao
: Multidrug resistance (MDR) of tumor cells is becoming the main reason for the failure of chemotherapy and P-glycoprotein (P-gp) mediated drug efflux has demonstrated to be the key factor for MDR. To address this issue, a novel pH-responsive mixed micelles drug delivery system composed of dextran-g-poly(lactide-co-glycolide)-g-histidine (HDP) and folate acid-D-α-tocopheryl polyethylene glycol 2000 (FA-TPGS2K) copolymers has been designed for the delivery of antitumor agent, paclitaxel (PTX) via FA-receptor mediated cell endocytosis, into PTX-resistant breast cancer MCF-7 cells (MCF-7/PTX)...
December 9, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27906043/exosomes-play-an-important-role-in-the-process-of-psoralen-reverse-multidrug-resistance-of-breast-cancer
#5
Xiaohong Wang, Chengfeng Xu, Yitong Hua, Leitao Sun, Kai Cheng, Zhongming Jia, Yong Han, Jianli Dong, Yuzhen Cui, Zhenlin Yang
BACKGROUND: Release of exosomes have been shown to play critical roles in drug resistance by delivering cargo. Targeting the transfer of exosomes from resistant cells to sensitive cells may be an approach to overcome some cases of drug resistance. METHOD: In this study, we investigated the potential role of exosomes in the process of psoralen reverse multidrug resistance of MCF-7/ADR cells. Exosomes were isolated by differential centrifugation of culture media from MCF-7/ADR cells (ADR/exo) and MCF-7 parental cells (S/exo)...
December 1, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27810353/pyrrolopyrimidine-derivatives-and-purine-analogs-as-novel-activators-of-multidrug-resistance-associated-protein-1-mrp1-abcc1
#6
Sven Marcel Schmitt, Katja Stefan, Michael Wiese
Multidrug resistance (MDR) is the main cause of diminished success in cancer chemotherapy. ABC transport proteins are considered to be one important factor of MDR. Besides P-glycoprotein (P-gp, ABCB1) and Breast Cancer Resistance Protein (BCRP, ABCG2), Multidrug Resistance-associated Protein 1 (MRP1, ABCC1) is associated with non-response to chemotherapy in different cancers. While considerable effort was spent in overcoming MDR during the last two decades, almost nothing is known with respect to activators of transport proteins...
January 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27779650/hoxb4-knockdown-reverses-multidrug-resistance-of-human-myelogenous-leukemia-k562-adm-cells-by-downregulating-p-gp-mrp1-and-bcrp-expression-via-pi3k-akt-signaling-pathway
#7
Hong Wang, Xiu-Hong Jia, Jie-Ru Chen, Ying-Jie Yi, Jian-Yong Wang, You-Jie Li, Shu-Yang Xie
Multidrug resistance (MDR) plays a pivotal role in human chronic myelogenous leukemia (CML) chemotherapy failure. MDR is mainly associated with the overexpression of drug efflux transporters of the ATP-binding cassette (ABC) proteins. Phosphoinositide 3-kinase (PI3K)/Akt signaling cascade is involved in the MDR phenotype and is correlated with multidrug resistance 1 (MDR1)/P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP) expression in many human malignancies...
December 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27754360/rack1-mediates-the-interaction-of-p-glycoprotein-with-anxa2-and-regulates-migration-and-invasion-of-multidrug-resistant-breast-cancer-cells
#8
Yi Yang, Na Wu, Zhiyong Wang, Fei Zhang, Ran Tian, Wei Ji, Xiubao Ren, Ruifang Niu
The emergence of multidrug resistance is always associated with more rapid tumor recurrence and metastasis. P-glycoprotein (P-gp), which is a well-known multidrug-efflux transporter, confers enhanced invasion ability in drug-resistant cells. Previous studies have shown that P-gp probably exerts its tumor-promoting function via protein-protein interaction. These interactions were implicated in the activation of intracellular signal transduction. We previously showed that P-gp binds to Anxa2 and promotes the invasiveness of multidrug-resistant (MDR) breast cancer cells through regulation of Anxa2 phosphorylation...
October 13, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27744704/one-step-self-assembling-nanomicelles-for-pirarubicin-delivery-to-overcome-multidrug-resistance-in-breast-cancer
#9
Yanping Li, Rui Li, Qinhui Liu, Wenyao Li, Ting Zhang, Min Zou, Hong Li, Tong Wu, Shihai Cheng, Zhiguang Su, Zhirong Zhang, Jinhan He
Tumor cells can acquire multidrug resistance (MDR) as a result of drug efflux mediated by P-glycoprotein (P-gp). Here we report a targeted delivery system to carry pirarubicin (THP) to MDR breast cancer both in vitro and in vivo. PEG-derivatized vitamin E (PAMV6) amphiphiles loaded with THP were self-assembled in a single step. The PAMV6 micelles showed unimodal size distribution and high drug loading efficiency. Cytotoxicity of PAMV6/THP was higher than that of free THP on MCF-7/ADR cells but comparable to that of THP on MCF-7 cells...
November 7, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27601896/synergistic-and-complete-reversal-of-the-multidrug-resistance-of-mitoxantrone-hydrochloride-by-three-in-one-multifunctional-lipid-sodium-glycocholate-nanocarriers-based-on-simultaneous-bcrp-and-bcl-2-inhibition
#10
Guixia Ling, Tianhong Zhang, Peng Zhang, Jin Sun, Zhonggui He
Multidrug resistance (MDR) is a severe obstacle to successful chemotherapy due to its complicated nature that involves multiple mechanisms, such as drug efflux by transporters (P-glycoprotein and breast cancer resistance protein, BCRP) and anti-apoptotic defense (B-cell lymphoma, Bcl-2). To synergistically and completely reverse MDR by simultaneous inhibition of pump and non-pump cellular resistance, three-in-one multifunctional lipid-sodium glycocholate (GcNa) nanocarriers (TMLGNs) have been designed for controlled co-delivery of water-soluble cationic mitoxantrone hydrochloride (MTO), cyclosporine A (CsA - BCRP inhibitor), and GcNa (Bcl-2 inhibitor)...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27596118/co-encapsulation-of-paclitaxel-and-baicalein-in-nanoemulsions-to-overcome-multidrug-resistance-via-oxidative-stress-augmentation-and-p-glycoprotein-inhibition
#11
Luhua Meng, Xuejun Xia, Yanfang Yang, Jun Ye, Wujun Dong, Panpan Ma, Yiqun Jin, Yuling Liu
Multidrug resistance (MDR) is a major obstacle for clinical application of paclitaxel (PTX). Recent studies have suggested that baicalein (BA) might be a potent MDR reversal agent with the ability of P-glycoprotein inhibition and oxidative stress augmentation. Herein, we co-encapsulated PTX and BA in nanoemulsions (PTX/BA NE) for overcoming MDR in breast cancer. Paclitaxel-cholesterol complex and baicalein-phospholipid complex were prepared to improve the liposolubility of PTX and BA. The cytotoxicity of the combination of PTX and BA with different weight ratios were evaluated and the combination with a weight ratio of 1/1 exhibited the strongest synergistic effect...
November 20, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27585695/grid-independent-descriptors-grind-analysis-and-sar-guided-molecular-docking-studies-to-probe-selectivity-profiles-of-inhibitors-of-multidrug-resistance-transporters-abcb1-and-abcg2
#12
Talha Shafi, Ishrat Jabeen
ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp, ABCB1) and breast cancer resistance protein (BCRP/ABCG2) are major determinant of pharmacokinetic, safety and efficacy profiles of drugs thereby effluxing a broad range of endogenous substances across the plasma membrane. Overexpression of these transporters in various tumors is also implicated in the development of multidrug resistance (MDR) and thus, hampers the success of cancer chemotherapy. Modulators of these efflux transporters in combination with chemotherapeutics could be a promising concept to increase the effective intracellular concentration of anticancer drugs...
August 31, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27581212/reversal-of-p-glycoprotein-mediated-multidrug-resistance-by-doxorubicin-and-quinine-co-loaded-liposomes-in-tumor-cells
#13
Qiying Shen, Liyan Qiu
Multidrug resistance (MDR) is a major obstacle to successful clinical cancer chemotherapy. Currently, there is still unsatisfactory demand for innovative strategies as well as effective and safe reversing agent to overcome MDR. In this study, we developed a novel nanoformulation, in which doxorubicin hydrochloride (DOX) and quinine hydrochloride (QN) were simultaneously loaded into liposomes by a pH-gradient method for overcoming MDR and enhancing cytotoxicity in a doxorubicin-resistant human breast cancer cell line (MCF-7/ADR)...
October 11, 2016: Journal of Liposome Research
https://www.readbyqxmd.com/read/27566201/a-myrsinol-diterpene-isolated-from-a-traditional-herbal-medicine-langdu-reverses-multidrug-resistance-in-breast-cancer-cells
#14
Huapeng Wang, Xiaobo Chen, Ting Li, Jing Xu, Yonggang Ma
ETHNOPHARMACOLOGICAL RELEVANCE: LANGDU, a Chinese traditional herbal medicine, was the dried roots of Euphorbia prolifera Buch-Ham. The herbal medicine has been used as anti-cancer and anti-inflammatory drug in local folk medicine for several hundred years. AIM OF THE STUDY: P-glycoprotein (P-gp) is a transmembrane exporter, which can expel a variety of anti-cancer drugs. Over-expressed P-glycoprotein in cancer cells impairs the effect of cancer chemotherapy and results in multidrug resistance (MDR)...
December 24, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27444552/reversal-of-multidrug-resistance-in-breast-cancer-mcf-7-adr-cells-by-h-r3-simdr1-pamam-complexes
#15
Jun Li, Jing Liu, Nana Guo, Xiaoning Zhang
Multidrug resistance (MDR) among breast cancer cells is the paramount obstacle for the successful chemotherapy. In this study, anti-EGFR antibody h-R3 was designed to self-assembled h-R3-siRNA-PAMAM-complexes (HSPCs) via electrostatic interactions for siRNA delivery. The physicochemical characterization, cell uptake, MDR1 silencing efficiency, cell migration, cell growth and cell apoptosis were investigated. The HSPCs presented lower cytotoxicity, higher cellular uptake and enhanced endosomal escape ability...
September 10, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27423937/selective-gpr55-antagonism-reduces-chemoresistance-in-cancer-cells
#16
Nagendra S Singh, Michel Bernier, Irving W Wainer
G protein-coupled receptor 55 (GPR55) possesses pro-oncogenic activity and its function can be competitively inhibited with (R,R')-4'-methoxy-1-naphthylfenoterol (MNF) through poorly defined signaling pathways. Here, the anti-tumorigenic effect of MNF was investigated in the human pancreatic cancer cell line, PANC-1, by focusing on the expression of known cancer biomarkers and the expression and function of multidrug resistance (MDR) exporters such as P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP)...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27418107/tki-combination-therapy-strategy-to-enhance-dasatinib-uptake-by-inhibiting-pgp-and-bcrp-mediated-efflux
#17
Ronilda D'Cunha, SoHyun Bae, Daryl J Murry, Guohua An
The overexpression of efflux transporters, especially P-glycoprotein (Pgp, MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2), represents an important mechanism of multidrug resistance (MDR). Tyrosine kinase inhibitors (TKIs), a novel group of target-specific anticancer drugs, have recently been found to interact with Pgp and BCRP and to serve as both substrates and inhibitors. Considering their dual role, we anticipate that combination TKI therapy may represent a promising strategy to reverse efflux transporter mediated TKI resistance...
October 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/27343697/reconstituted-high-density-lipoprotein-mediated-targeted-co-delivery-of-hz08-and-paclitaxel-enhances-the-efficacy-of-paclitaxel-in-multidrug-resistant-mcf-7-breast-cancer-cells
#18
Fangrong Zhang, Xiaoyi Wang, Xiangting Xu, Min Li, Jianping Zhou, Wei Wang
In the past decades, reconstituted high density lipoprotein (rHDL) has been successfully developed as a drug carrier since the enhanced HDL-lipids uptake is demonstrated in several human cancers. In this paper, rHDL, for the first time, was utilized to co-encapsulate two hydrophobic drugs: an anticancer drug, paclitaxel (PTX), and a new reversal agent for P-gp (P-glycoprotein)-mediated multidrug resistance (MDR) of cancer, N-cyano-1-[(3,4-dimethoxyphenyl)methyl]-3,4-dihydro-6,7-dimethoxy-N'-octyl-2(1H)-isoquinoline-carboximidamide (HZ08)...
September 20, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27300692/role-of-human-breast-cancer-related-protein-versus-p-glycoprotein-as-an-efflux-transporter-for-benzylpenicillin-potential-importance-at-the-blood-brain-barrier
#19
Yangfang Li, Qian Wu, Chen Li, Ling Liu, Kun Du, Jin Shen, Yuqin Wu, Xiaofen Zhao, Mei Zhao, Lingyun Bao, Jin Gao, Richard F Keep, Jianming Xiang
While the blood-brain barrier (BBB) protects the brain by controlling the access of solutes and toxic substances to brain, it also limits drug entry to treat central nervous system disorders. Many drugs are substrates for ATP-binding cassette (ABC) transporters at the BBB that limit their entry into the brain. The role of those transporters in limiting the entry of the widely prescribed therapeutic, benzylpenicillin, has produced conflicting results. This study investigated the possible potential involvement of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), two ABC transporters, in benzylpenicillin transport at BBB in human using MDCKII cells overexpressing those transporters as well as pharmacological inhibition...
2016: PloS One
https://www.readbyqxmd.com/read/27250110/sensitization-of-multidrug-resistant-malignant-cells-by-liposomes-co-encapsulating-doxorubicin-and-chloroquine-through-autophagic-inhibition
#20
Menghua Gao, Yuzhen Xu, Liyan Qiu
Adenosine triphosphate (ATP)-binding cassette (ABC) transporters play a key role in the development of multidrug resistance (MDR) in cancer cells. P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1) are important proteins in this superfamily which are widely expressed on the membranes of multidrug resistance (MDR) cancer cells. Besides, upregulation of cellular autophagic responses is considered a contributing factor for MDR in cancer cells. We designed a liposome system co-encapsulating a chemotherapeutic drug (doxorubicin hydrochloride, DOX) and a typical autophagy inhibitior (chloroquine phosphate, CQ) at a weight ratio of 1:2 and investigated its drug resistance reversal mechanism...
June 2, 2016: Journal of Liposome Research
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