A semisynthetic taxane Yg-3-46a effectively evades P-glycoprotein and β-III tubulin mediated tumor drug resistance in vitro

2013 ◽  
Vol 341 (2) ◽  
pp. 214-223 ◽  
Author(s):  
Pei Cai ◽  
Peihua Lu ◽  
Frances J. Sharom ◽  
Wei-Shuo Fang
Keyword(s):  
Drug Resistance ◽  
P Glycoprotein ◽  
Tumor Drug Resistance

scholarly journals Degradation of P-glycoprotein by pristimerin contributes to overcoming ABCB1-mediated chemotherapeutic drug resistance in vitro

2016 ◽  
Vol 37 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Yan-Yan Yan ◽  
Fang Wang ◽  
Xiao-Qin Zhao ◽  
Xiao-Kun Wang ◽  
Yi-Fan Chen ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Chemotherapeutic Drug ◽  
P Glycoprotein

scholarly journals Artificial microenvironment of in vitro glioblastoma cell cultures changes profile of miRNAs related to tumor drug resistance

2019 ◽  
Vol Volume 12 ◽  
pp. 3905-3918
Author(s):  
Monika Witusik-Perkowska ◽  
Magdalena Zakrzewska ◽  
Dariusz Jaskolski ◽  
Paweł P Liberski ◽  
Janusz Szemraj
Keyword(s):  
Drug Resistance ◽  
Cell Cultures ◽  
Glioblastoma Cell ◽  
Tumor Drug Resistance

An Update on Circumventing Multidrug Resistance in Cancer by Targeting P-Glycoprotein

2018 ◽  
Vol 18 (7) ◽  
pp. 677-696 ◽  
Author(s):  
Xiaoqian Yang ◽  
Xiaoduan Li ◽  
Zhenfeng Duan ◽  
Xipeng Wang
Keyword(s):  
Drug Resistance ◽  
Clinical Trials ◽  
Multidrug Resistance ◽  
Chemotherapeutic Agents ◽  
Attractive Potential ◽  
Special Focus ◽  
Drug Resistant ◽  
Patients With Cancer ◽  
P Glycoprotein

Background: The ultimate emergence of multidrug resistance remains a severe limitation of chemotherapy treatment for patients with cancer. The best-characterized cause of drug resistance involves the overexpression of P-glycoprotein (Pgp), which decreases the intracellular accumulation of chemotherapeutic agents in drug-resistant cancer cells. Thus, Pgp has become an attractive potential target for treating chemotherapy-resistant cancer, but the outcomes of using chemotherapy in combination with Pgp inhibitors in clinical trials to date have been disappointing. Objective: We herein examine the relationship between Pgp and drug resistance and update the strategies for overcoming drug resistance by targeting Pgp, with a special focus on the recent progress in the area of preventing the development of drug resistance by targeting Pgp both in vitro and in vivo. Given the essential roles of drug-resistant cancer models in these investigations, commonly used approaches for establishing drug-resistant models in the laboratory are also addressed. Conclusion: Considering the roles of Pgp in normal physiological conditions and its appreciated roles in detoxification, the currently available Pgp inhibitors undoubtedly cannot be used to reverse drug resistance in the clinic. Although agents that target Pgp to prevent and/or reverse drug resistance are not beneficial at the doses used in the laboratory when administered to patients with cancer who are enrolled in clinical trials, compounds targeting Pgp are widely acknowledged to be promising for circumventing drug resistance.

scholarly journals Relationship Between Major Vault Protein/Lung Resistance Protein, Multidrug Resistance-Associated Protein, P-Glycoprotein Expression, and Drug Resistance in Childhood Leukemia

Blood ◽  
1998 ◽  
Vol 91 (6) ◽  
pp. 2092-2098 ◽  
Author(s):  
M.L. den Boer ◽  
R. Pieters ◽  
K.M. Kazemier ◽  
M.M.A. Rottier ◽  
C.M. Zwaan ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Childhood Leukemia ◽  
Lymphoblastic Leukemia ◽  
Major Vault Protein ◽  
Lung Resistance Protein ◽  
P Glycoprotein ◽  
Lung Resistance ◽  
Resistance Protein

Cellular drug resistance is related to a poor prognosis in childhood leukemia, but little is known about the underlying mechanisms. We studied the expression of P-glycoprotein (P-gp), multidrug resistance (MDR)-associated protein (MRP), and major vault protein/lung resistance protein (LRP) in 141 children with acute lymphoblastic leukemia (ALL) and 27 with acute myeloid leukemia (AML) by flow cytometry. The expression was compared between different types of leukemia and was studied in relation with clinical risk indicators and in vitro cytotoxicity of the MDR-related drugs daunorubicin (DNR), vincristine (VCR), and etoposide (VP16) and the non–MDR-related drugs prednisolone (PRD) and L-asparaginase (ASP). In ALL, P-gp, MRP, and LRP expression did not differ between 112 initial and 29 unrelated relapse samples nor between paired initial and relapse samples from 9 patients. In multiple relapse samples, LRP expression was 1.6-fold higher compared with both initial (P = .026) and first relapse samples (P = .050), which was not observed for P-gp and MRP. LRP expression was weakly but significantly related to in vitro resistance to DNR (Spearman's rank correlation coefficient 0.25, P = .016) but not to VCR, VP16, PRD, and ASP. No significant correlations were found between P-gp or MRP expression and in vitro drug resistance. Samples with a marked expression of two or three resistance proteins did not show increased resistance to the tested drugs compared with the remaining samples. The expression of P-gp, MRP, and LRP was not higher in initial ALL patients with prognostically unfavorable immunophenotype, white blood cell count, or age. The expression of P-gp and MRP in 20 initial AML samples did not differ or was even lower compared with 112 initial ALL samples. However, LRP expression was twofold higher in the AML samples (P < .001), which are more resistant to a variety of drugs compared with ALL samples. In conclusion, P-gp and MRP are unlikely to be involved in drug resistance in childhood leukemia. LRP might contribute to drug resistance but only in specific subsets of children with leukemia.

scholarly journals Relationship Between Major Vault Protein/Lung Resistance Protein, Multidrug Resistance-Associated Protein, P-Glycoprotein Expression, and Drug Resistance in Childhood Leukemia

Blood ◽  
1998 ◽  
Vol 91 (6) ◽  
pp. 2092-2098 ◽  
Author(s):  
M.L. den Boer ◽  
R. Pieters ◽  
K.M. Kazemier ◽  
M.M.A. Rottier ◽  
C.M. Zwaan ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Childhood Leukemia ◽  
Lymphoblastic Leukemia ◽  
Major Vault Protein ◽  
Lung Resistance Protein ◽  
P Glycoprotein ◽  
Lung Resistance ◽  
Resistance Protein

Abstract Cellular drug resistance is related to a poor prognosis in childhood leukemia, but little is known about the underlying mechanisms. We studied the expression of P-glycoprotein (P-gp), multidrug resistance (MDR)-associated protein (MRP), and major vault protein/lung resistance protein (LRP) in 141 children with acute lymphoblastic leukemia (ALL) and 27 with acute myeloid leukemia (AML) by flow cytometry. The expression was compared between different types of leukemia and was studied in relation with clinical risk indicators and in vitro cytotoxicity of the MDR-related drugs daunorubicin (DNR), vincristine (VCR), and etoposide (VP16) and the non–MDR-related drugs prednisolone (PRD) and L-asparaginase (ASP). In ALL, P-gp, MRP, and LRP expression did not differ between 112 initial and 29 unrelated relapse samples nor between paired initial and relapse samples from 9 patients. In multiple relapse samples, LRP expression was 1.6-fold higher compared with both initial (P = .026) and first relapse samples (P = .050), which was not observed for P-gp and MRP. LRP expression was weakly but significantly related to in vitro resistance to DNR (Spearman's rank correlation coefficient 0.25, P = .016) but not to VCR, VP16, PRD, and ASP. No significant correlations were found between P-gp or MRP expression and in vitro drug resistance. Samples with a marked expression of two or three resistance proteins did not show increased resistance to the tested drugs compared with the remaining samples. The expression of P-gp, MRP, and LRP was not higher in initial ALL patients with prognostically unfavorable immunophenotype, white blood cell count, or age. The expression of P-gp and MRP in 20 initial AML samples did not differ or was even lower compared with 112 initial ALL samples. However, LRP expression was twofold higher in the AML samples (P < .001), which are more resistant to a variety of drugs compared with ALL samples. In conclusion, P-gp and MRP are unlikely to be involved in drug resistance in childhood leukemia. LRP might contribute to drug resistance but only in specific subsets of children with leukemia.

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