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P-glycoprotein breast cancer mdr

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https://www.readbyqxmd.com/read/29737828/light-activated-ros-responsive-nanoplatform-co-delivering-apatinib-and-doxorubicin-for-enhanced-chemo-photodynamic-therapy-of-multidrug-resistant-tumors
#1
Xiao Wei, Lingqiao Liu, Xing Guo, Yi Wang, Jingya Zhao, Shaobing Zhou
Cancer chemotherapy faces the problem of the multidrug resistance (MDR) of tumor cells, which is a puzzling issue that leads to treatment failure. To address it, an innovative approach is proposed to construct a light-activated reactive oxygen species (ROS)-responsive nanoplatform based on a protoporphyrin (PpIX)-conjugated and dual chemotherapeutics-loaded polymer micelle. This system combines chemotherapy and photodynamic therapy (PDT) to defeat the MDR of tumors. Such an intelligent nanocarrier can prolong the blood circulation due to the negatively charged polysaccharide component of chondroitin sulfate (CS) and subsequently being selectively internalized by DOX-resistant human breast cancer MCF-7 cells (MCF-7/ADR)...
May 8, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29704644/effect-of-%C3%AE-elemene-on-the-kinetics-of-intracellular-transport-of-d-luciferin-potassium-salt-abc-substrate-in-doxorubicin-resistant-breast-cancer-cells-and-the-associated-molecular-mechanism
#2
Chao-Yuan Tang, Li-Xin Zhu, Jian-Dong Yu, Zhi Chen, Man-Cang Gu, Chao-Feng Mu, Qi Liu, Yang Xiong
In order to explore the mechanism of the reversing multidrug resistance (MDR) phenotypes by β-elemene (β-ELE) in doxorubicin (DOX)-resistant breast cancer cells (MCF-7/DOX), both the functionality and quantity of the ABC transporters in MCF-7/DOX were studied. Bioluminescence imaging (BLI) was used to study the efflux of d-luciferin potassium salt, the substrate of ATP-binding cassette transporters (ABC transporters), in MCF-7/DOX cells treated by β-ELE. At the same time three major ABC transport proteins and genes-related MDR, P-glycoprotein (P-gp, ABCB1) and multidrug resistance-associated protein 1 (MRP, ABCC1) as well as breast cancer resistance protein (BCRP, ABCG2) were analyzed by q-PCR and Western blot...
April 25, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29694920/a-polypeptide-based-podophyllotoxin-conjugate-for-the-treatment-of-multi-drug-resistant-breast-cancer-with-enhanced-efficiency-and-minimal-toxicity
#3
Huicong Zhou, Shixian Lv, Dawei Zhang, Mingxiao Deng, Xuefei Zhang, Zhaohui Tang, Xuesi Chen
Podophyllotoxin (PPT) is a chemotherapeutic agent which has shown significant activity against P-glycoprotein (P-gp) mediated multi drug resistant cancer cells. However, because of the poor aqueous solubility and high toxicity, PPT cannot be used in clinical cancer therapy. In order to enhance the efficiency and reduce side effect of PPT, a polypeptide based PPT conjugate PLG-g-mPEG-PPT was developed and used for the treatment of multi drug resistant breast cancer. The PLG-g-mPEG-PPT was prepared by conjugating PPT to poly(L-glutamic acid)-g-methoxy poly(ethylene glycol) (PLG-g-mPEG) via ester bonds...
April 22, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29671072/reversion-of-multidrug-resistance-by-co-encapsulation-of-doxorubicin-and-metformin-in-poly-lactide-co-glycolide-d-%C3%AE-tocopheryl-polyethylene-glycol-1000-succinate-nanoparticles
#4
Vahid Shafiei-Irannejad, Nasser Samadi, Roya Salehi, Bahman Yousefi, Mahdi Rahimi, Abolfazl Akbarzadeh, Nosratollah Zarghami
PURPOSE: P-glycoprotein (P-gp) mediated multidrug resistance (MDR) has been recognized as the main obstacle against successful cancer treatment. To address this problem, co-encapsulated doxorubicin (DOX) and metformin (Met) in a biodegradable polymer composed of poly(lactide-co-glycolide) (PLGA) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was prepared. We reported in our previous study that Met inhibits P-gp in DOX resistant breast cancer (MCF-7/DOX) cells. TPGS is a bioactive compound which has also been shown to inhibit P-gp, further to its pharmaceutical advantages...
April 18, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29663807/reversing-multidrug-resistance-by-multiplexed-gene-silencing-for-enhanced-breast-cancer-chemotherapy
#5
Yanli Li, Xiaonan Gao, Zhengze Yu, Bo Liu, Wei Pan, Na Li, Bo Tang
Multidrug resistance (MDR), as one of the main problems in clinical breast cancer chemotherapy, is closely related with the overexpression of drug efflux transporter P-glycoprotein (P-gp). In this study, a novel drug-loaded nanosystem was developed for inhibiting the P-gp expression and reversing multidrug resistance by multiplexed gene silencing, which composes of graphene oxide (GO) modified with two molecular beacons (MBs) and Doxorubicin (Dox). When the nanosystem was uptaken by the MDR breast cancer cells, Dox was released in the acidic endosomes and MBs were hybridized with target sequences...
April 17, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29655913/germacrone-reverses-adriamycin-resistance-in-human-chronic-myelogenous-leukemia-k562-adm-cells-by-suppressing-mdr1-gene-p-glycoprotein-expression
#6
Jia Pan, Dong Miao, Li Chen
Multidrug resistance (MDR) usually causes chemotherapy failure of chronic myelogenous leukemia (CML). Germacrone is a terpenoid compound and has been reported to reverse MDR in breast cancer cells. However, the effect of germacrone on MDR in CML cells was unknown. The aim of the present study was to evaluate the effect of germacrone on MDR in adriamycin resistance of CML cells. Treatment with a combination of germacrone and adriamycin synergistically inhibited the viability and increased LDH release in K562/ADM cells...
April 12, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29606866/surfactin-based-nanoparticles-loaded-with-doxorubicin-to-overcome-multidrug-resistance-in-cancers
#7
Wenjing Huang, Yan Lang, Abdul Hakeem, Yan Lei, Lu Gan, Xiangliang Yang
Background: Multidrug resistance (MDR) is one of the major obstacles to successful cancer chemotherapy. Developing efficient strategies to reverse MDR remains a major challenge. Surfactin (SUR), a cyclic lipopeptide biosurfactant, has been found to display anticancer activity. Methods: In this paper, SUR was assembled by solvent-emulsion method to load the anticancer drug doxorubicin (DOX). The cytotoxicity of DOX-loaded SUR nanoparticles (DOX@SUR) against DOX-resistant human breast cancer MCF-7/ADR is measured by MTT assay...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29547875/elucidation-of-chemosensitization-effect-of-acridones-in-cancer-cell-lines-combined-pharmacophore-modeling-3d-qsar-and-molecular-dynamics-studies
#8
Deepak Reddy Gade, Amareswararao Makkapati, Rajesh Babu Yarlagadda, Godefridus J Peters, B S Sastry, V V S Rajendra Prasad
Overexpression of P-glycoprotein (P-gp) leads to the emergence of multidrug resistance (MDR) in cancer treatment. Acridones have the potential to reverse MDR and sensitize cells. In the present study, we aimed to elucidate the chemosensitization potential of acridones by employing various molecular modelling techniques. Pharmacophore modeling was performed for the dataset of chemosensitizing acridones earlier proved for cytotoxic activity against MCF7 breast cancer cell line. Gaussian-based QSAR studies also performed to predict the favored and disfavored region of the acridone molecules...
February 24, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29523600/a-promising-microtubule-inhibitor-deoxypodophyllotoxin-exhibits-better-efficacy-to-multi-drug-resistant-breast-cancer-than-paclitaxel-via-avoiding-efflux-transport
#9
Xiaojie Zang, Guangji Wang, Qinngyun Cai, Xiao Zheng, Jingwei Zhang, Qianying Chen, Baojin Wu, Xiong Zhu, Haiping Hao, Fang Zhou
Multi-drug resistance (MDR) is a common limitation for the clinical use of microtubule-targeting chemotherapeutic agents and it is the main factor for poor prognoses in cancer therapy. Here, we report on deoxypodophyllotoxin (DPT), a promising microtubule inhibitor in phase I, as a promising candidate to circumvent the obstacle. DPT remarkably suppressed the tumor growth in xenograft mice bearing either Paclitaxel (PTX)-sensitive MCF-7/S or acquired resistance MCF-7/Adr (MCF-7/A) cells. Also, DPT exhibited a similar accumulation in both tumors, while PTX displayed much a lower accumulation in the resistant tumors...
March 9, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29484330/overcoming-drug-resistant-lung-cancer-by-paclitaxel-loaded-tetrahedral-dna-nanostructures
#10
X Xie, X Shao, W Ma, D Zhao, S Shi, Q Li, Y Lin
Paclitaxel (PTX) is an effective drug against diseases such as lung cancer, ovarian cancer, and breast cancer. However, multidrug resistance limits the clinical applications of this drug. Tetrahedral DNA nanostructures (TDNs) offer great promise as a drug delivery candidate. In our study, we prepared TDNs that were subsequently loaded with PTX (PTX/TDNs). The cytotoxicity of PTX/TDNs and PTX alone on non-small cell lung cancer (NSCLC) cells (A549) and the PTX-resistant cell line (A549/T) was determined using a cell count kit-8 (CCK-8) assay...
March 28, 2018: Nanoscale
https://www.readbyqxmd.com/read/29407947/jatrophane-diterpenoids-from-euphorbia-sororia-as-potent-modulators-against-p-glycoprotein-based-multidrug-resistance
#11
Rui Hu, Jie Gao, Rushangul Rozimamat, Haji Akber Aisa
Five new (1-5) and ten known (6-15) jatrophane diterpenoids were isolated from the fructus of Euphorbia sororia and their structures were elucidated by extensive spectroscopic analysis. The absolute configurations of compounds 1 and 4 were confirmed by X-ray crystallographic analysis. Cytotoxicity and anti-multidrug resistance effects of these jatrophane diterpenoids were evaluated in multidrug-resistant MCF-7/ADR breast cancer cells with an overexpression of P-glycoprotein (P-gp). Eight compounds (1, 2, 4, 6, 8, 10, 11, and 15) showed promising chemoreversal abilities compared to verapamil (VRP)...
February 25, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29399166/association-between-twist-and-multidrug-resistance-gene-associated-proteins-in-taxol-%C3%A2-resistant-mcf-7-cells-and-a-293-cell-model-of-twist-overexpression
#12
Li Wang, Rui-Zhi Tan, Zhi-Xia Zhang, Rui Yin, Yong-Liang Zhang, Wei-Jia Cui, Tao He
Multidrug resistance (MDR) severely limits the effectiveness of chemotherapy. Previous studies have identified Twist as a key factor of acquired MDR in breast, gastric and prostate cancer. However, the underlying mechanisms of action of Twist in MDR remain unclear. In the present study, the expression levels of MDR-associated proteins, including lung resistance-related protein (LRP), topoisomerase IIα (TOPO IIα), MDR-associated protein (MRP) and P-glycoprotein (P-gp), and the expression of Twist in cancerous tissues and pericancerous tissues of human breast cancer, were examined...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29368443/barbigerone-reverses-multidrug-resistance-in-breast-mcf-7-adr-cells
#13
Xiuxia Li, Li Wan, Fang Wang, Heying Pei, Li Zheng, Wenshuang Wu, Haoyu Ye, Yanping Wang, Lijuan Chen
Development of agents to overcome multidrug resistance (MDR) is one of the important strategies in cancer chemotherapy, and P-glycoprotein (P-gp) correlates with the degree of resistance. As a naturally occurring isoflavone, whether barbigerone (BA) could reverse MDR, is unknown. In this paper, we evaluated effects of BA on reversing P-gp mediated MDR of adriamycin (ADR)-resistant human breast carcinoma (MCF-7/ADR) cells. BA (0.5 μM) treatment showed strong potency to increase ADR cytotoxicity toward MCF-7/ADR cells...
January 24, 2018: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29303075/abc-transporters-regulation-and-association-with-multidrug-resistance-in-hepatocellular-carcinoma-and-colorectal-carcinoma
#14
María Paula Ceballos, Juan Pablo Rigalli, Lucila Ines Cere, Mariana Semeniuk, Viviana Alicia Catania, Maria Laura Ruiz
For most cancers, the treatment of choice is still being chemotherapy despite of its severe adverse effects, systemic toxicity and limited efficacy due to the development of multidrug resistance (MDR). MDR leads to chemotherapy failure generally associated with a decrease in drug concentration inside cancer cells, frequently due to an overexpression of ABC transporters such as P-glycoprotein (P-gp/MDR1/ABCB1), multidrug resistance-associated proteins (MRPs/ABCCs), and breast cancer resistance protein (BCRP/ABCG2) that limit the efficacy of chemotherapeutic drugs...
January 4, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29181822/schisandrin-a-reverses-doxorubicin-resistant-human-breast-cancer-cell-line-by-the-inhibition-of-p65-and-stat3-phosphorylation
#15
Zong-Lin Zhang, Qing-Cheng Jiang, Su-Rong Wang
BACKGROUND: Multidrug resistance (MDR) in breast cancer therapy occurs frequently. Thus, anti-MDR agents from natural products or synthetic compounds were tested extensively. We have also explored the reverse effect and mechanism of Schisandrin A (Sch A), a natural product, on MCF-7 breast cancer doxorubicin (DOX)-resistant subline MCF-7/DOX. METHODS: MTT assay was performed to measure the viability of MCF-7 cells to assess the reverse effect of Sch A. Western blot analysis was used to study the protein levels...
March 2018: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/29181060/expression-of-multidrug-resistance-protein-p-glycoprotein-in-correlation-with-markers-of-hypoxia-hif-1%C3%AE-epo-epo-r-in-invasive-breast-cancer-with-metastasis-to-lymph-nodes
#16
Anna M Badowska-Kozakiewicz, Maria Sobol, Janusz Patera
Introduction: Overexpression of the mdr-1 gene is the earliest discovered mechanism of multidrug resistance, which is associated with P-glycoprotein (P-gp) - a cell membrane protein responsible for the efflux of drugs of various structures out of cancer cells. Although the expression of P-glycoprotein has been demonstrated in many cancer types, its relation to markers of hypoxia such as HIF-1α, EPO-R or EPO in invasive breast cancer is not well established. The aim of this research was to analyze the co-expression of P-glycoprotein and the markers of tissue hypoxia HIF-1α, EPO, and EPO-R by immunohistochemistry in invasive breast cancer classified according to the presence of steroid receptors and the HER2 receptors...
October 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/29077148/the-effect-of-saikosaponin-d-on-doxorubicin-pharmacokinetics-and-its-mdr-reversal-in-mcf-7-adr-cell-xenografts
#17
C Li, H-G Xue, L-J Feng, M-L Wang, P Wang, X-D Gai
OBJECTIVE: Multidrug resistance (MDR) is a major cause of chemotherapy failure in the treatment of cancer patients. This study aimed to determine whether saikosaponin D (SSd) can enhance the efficacy of the anticancer drug doxorubicin (Dox) both in vitro and in vivo and whether SSd can alter Dox pharmacokinetics in the serum of mice. MATERIALS AND METHODS: MCF-7/adr cells were used to investigate the effect of SSd on reversing MDR. Cell viability was assessed by MTT assay...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29050217/triterpenoids-from-aglaia-abbreviata-exert-cytotoxicity-and-multidrug-resistant-reversal-effect-in-mcf-7-adm-cells-via-reactive-oxygen-species-induction-and-p-glycoprotein-inhibition
#18
Juan Cen, Beibei Zheng, Rubing Bai, Li Zhang, Feng Zhang, Xia Zhang
Triterpenoids from the Aglaia have been shown cytotoxicity on a broad spectrum of human tumor cells. In the present study, we extracted triterpenoids AA-5 (1) and AA-6 (2) from stems of Aglaia abbreviata , and studied their cytotoxicity in multidrug resistant (MDR) MCF-7/ADM cells. After 48 h treatment, AA-5 (1) and AA-6 (2) significantly increased mitochondrial-mediated apoptosis by enhancing reactive oxygen species (ROS) with depressed mitochondrial membrane potential and caspase-9 activities. The drug efflux transporter P-glycoprotein (P-gp) and the intracellular antioxidant systems, involving Glutathione S-Transferase π, Glutathione and heme oxygenase-1, were also inhibited via the ROS-depressed Akt/NF-E2-related factor 2 pathway...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29016119/9-deazapurines-as-broad-spectrum-inhibitors-of-the-abc-transport-proteins-p-glycoprotein-multidrug-resistance-associated-protein-1-and-breast-cancer-resistance-protein
#19
Katja Stefan, Sven Marcel Schmitt, Michael Wiese
P-Glycoprotein (P-gp, ABCB1), multidrug resistance-associated protein 1 (MRP1, ABCC1), and breast cancer resistance protein (BCRP, ABCG2) are the three major ABC transport proteins conferring resistance to many structurally diverse anticancer agents, leading to the phenomenon called multidrug resistance (MDR). Much effort has been put into the development of clinically useful compounds to reverse MDR. Broad-spectrum inhibitors of ABC transport proteins can be of great use in cancers that simultaneously coexpress two or three transporters...
November 9, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28987325/anti-tumor-compound-ry10-4-suppresses-multidrug-resistance-in-mcf-7-adr-cells-by-inhibiting-pi3k-akt-nf-%C3%AE%C2%BAb-signaling
#20
Xiaofan Yang, Yufeng Ding, Miao Xiao, Xin Liu, Jinlan Ruan, Pingping Xue
RY10-4, an anti-tumor agent, exerts cytotoxicity to various human cancer cell lines. However, few studies reported the effect of combined application of RY10-4 and chemotherapeutic drugs against cancer cells with multidrug resistance (MDR). In this study, P-glycoprotein (P-gp), which is reported to mediate MDR to anti-cancer drugs, was proved to be overexpressed in the adriamycin (ADR)-resistant human breast cancer cells, namely MCF-7/ADR cells. Furthermore, RY10-4 application resulted in a downregulation of P-gp in MCF-7/ADR cells, thus leading to higher chemosensitivity to ADR...
December 25, 2017: Chemico-biological Interactions
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