The role of multi-drug resistance p-glycoprotein in glucocorticoid function: Studies in animals and relevance in humans

2008 ◽  
Vol 583 (2-3) ◽  
pp. 263-271 ◽  
Author(s):  
Carmine M. Pariante
Keyword(s):  
Drug Resistance ◽  
Multi Drug Resistance ◽  
P Glycoprotein

scholarly journals Autocrine IL-6/STAT3 signaling aids development of acquired drug resistance in Group 3 medulloblastoma

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Lakshana Sreenivasan ◽  
Hui Wang ◽  
Shyong Quin Yap ◽  
Pascal Leclair ◽  
Anthony Tam ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multi Drug Resistance ◽  
Acquired Drug Resistance ◽  
Stat3 Signaling ◽  
Therapeutic Benefits ◽  
Signaling Axis ◽  
Neuronal Precursors ◽  
Cranial Fossa ◽  
Group 3

AbstractMedulloblastoma (MB) is a high-grade pediatric brain malignancy that originates from neuronal precursors located in the posterior cranial fossa. In this study, we evaluated the role of STAT3 and IL-6 in a tumor microenvironment mediated drug resistance in human MBs. We established that the Group 3 MB cell line, Med8A, is chemosensitive (hence Med8A-S), and this is correlated with a basal low phosphorylated state of STAT3, while treatment with IL-6 induced robust increases in pY705-STAT3. Via incremental selection with vincristine, we derived the stably chemoresistant variant, Med8A-R, that exhibited multi-drug resistance, enhanced IL-6 induced pY705-STAT3 levels, and increased IL6R expression. Consequently, abrogation of STAT3 or IL6R expression in Med8A-R led to restored chemosensitivity to vincristine, highlighting a prominent role for canonical IL-6/STAT3 signaling in acquired drug resistance. Furthermore, Med8A-S subjected to conditioning exposure with IL-6, termed Med8A-IL6+ cells, exhibited enhanced vincristine resistance, increased expression of pY705-STAT3 and IL6R, and increased secretion of IL-6. When cocultured with Med8A-IL6+ cells, Med8A-S cells exhibited increased pY705-STAT3 and increased IL-6 secretion, suggesting a cytokine feedback loop responsible for amplifying STAT3 activity. Similar IL-6 induced phenomena were also observed in the Group 3 MB cell lines, D283 and D341, including increased pY705-STAT3, drug resistance, IL-6 secretion and IL6R expression. Our study unveiled autocrine IL-6 as a promoter of STAT3 signaling in development of drug resistance, and suggests therapeutic benefits for targeting the IL-6/STAT3 signaling axis in Group 3 MBs.

Synthesis and Biological Evaluation of C-Aromataxane Derivatives as P-Glycoprotein-Mediated Multi Drug Resistance Reversal Agents

Heterocycles ◽  
2015 ◽  
Vol 90 (1) ◽  
pp. 482
Author(s):  
Takayuki Doi ◽  
Naoko Yamaguchi ◽  
Kosuke Ohsawa ◽  
Kazuoki Nakai ◽  
Masahito Yoshida ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Biological Evaluation ◽  
Multi Drug Resistance ◽  
Reversal Agents ◽  
P Glycoprotein ◽  
Resistance Reversal ◽  
Synthesis And Biological Evaluation

scholarly journals CD44 promotes multi-drug resistance by protecting P-glycoprotein from FBXO21-mediated ubiquitination

Oncotarget ◽  
2015 ◽  
Vol 6 (28) ◽  
pp. 26308-26321 ◽  
Author(s):  
Abhilash K. Ravindranath ◽  
Swayamjot Kaur ◽  
Roman P. Wernyj ◽  
Muthu N. Kumaran ◽  
Karl E. Miletti-Gonzalez ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multi Drug Resistance ◽  
P Glycoprotein

PEAK1 promotes invasion and metastasis and confers drug resistance in breast cancer

2021 ◽  
Author(s):  
xingang wang ◽  
YAN ZHENG ◽  
YU WANG
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cell Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Multi Drug Resistance ◽  
Cancer Tissues

Abstract Background and AimsPseudopodium-enriched atypical kinase 1 (PEAK1) has reported to be upregulated in human malignancies and related with poor prognosis. Enhanced PEAK1 expression facilitates tumor cell survival, invasion, metastasis and chemoresistance. However, the role of PEAK1 in breast cancer is not clear. Here, we investigated the PEAK1 expression in breast cancer and analyzed its relation with clinicopathological status and chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated the role of PEAK1 on breast cancer cells in vitro and in vivo. MethodsImmunohistochemistry (IHC) was performed in 112 surgical resected breast cancer tissues. The associations between clinicopathological status, multi-drug resistance and PEAK1 expression were determined. Effect of PEAK1 overexpression or down-expression on proliferation, colony formation, invasion, migration, metastasis and Doxorubicin sensitivity in the MCF-7 cells in vitro and in vivo was detected. ResultsPEAK1 was overexpressed in breast cancer tissues and NAC -resistant breast cancer tissues. High PEAK1 expression was related with tumor size, high tumor grade, T stage, LN metastasis, recurrence, Ki-67 expression, Her-2 expression and multi-drug resistance. Targeting PEAK1 inhibited cell growth, invasion, metastasis and reversed chemoresistance to Doxorubicin in breast cancer cells in vitro and in vivo. ConclusionHigh PEAK1 expression was associated with invasion, metastasis and chemoresistance of breast cancers. Furthermore, targeting PEAK1 could inhibit cell growth and metastasis, and reverse chemoresistance in breast cancer cells, which provides an effective treatment strategies for breast cancer.

scholarly journals Grape Seed Procyanidin Reversal of P-glycoprotein Associated Multi-Drug Resistance via Down-regulation of NF-κB and MAPK/ERK Mediated YB-1 Activity in A2780/T Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e71071 ◽  
Author(s):  
Bo-xin Zhao ◽  
Ya-bin Sun ◽  
Sheng-qi Wang ◽  
Lian Duan ◽  
Qi-lu Huo ◽  
...  
Keyword(s):  
Drug Resistance ◽  
T Cells ◽  
Grape Seed ◽  
Multi Drug Resistance ◽  
Down Regulation ◽  
P Glycoprotein

scholarly journals Clitocine Reversal of P-Glycoprotein Associated Multi-Drug Resistance through Down-Regulation of Transcription Factor NF-κB in R-HepG2 Cell Line

PLoS ONE ◽  
2012 ◽  
Vol 7 (8) ◽  
pp. e40720 ◽  
Author(s):  
Jianguo Sun ◽  
Chilam Au Yeung ◽  
Ngai Na Co ◽  
Tsun Yee Tsang ◽  
Esmond Yau ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Transcription Factor ◽  
Cell Line ◽  
Hepg2 Cell ◽  
Multi Drug Resistance ◽  
Regulation Of Transcription ◽  
Hepg2 Cell Line ◽  
Down Regulation ◽  
P Glycoprotein

scholarly journals Cancer drug pan-resistance: pumps, cancer stem cells, quiescence, epithelial to mesenchymal transition, blocked cell death pathways, persisters or what?

Open Biology ◽  
2012 ◽  
Vol 2 (5) ◽  
pp. 120066 ◽  
Author(s):  
Piet Borst
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Epithelial To Mesenchymal Transition ◽  
Residual Disease ◽  
Cancer Drug ◽  
Multi Drug Resistance ◽  
Mesenchymal Transition ◽  
Cell Death Pathways ◽  
P Glycoprotein ◽  
Mouse Tumour

Although chemotherapy of tumours has scored successes, drug resistance remains the major cause of death of cancer patients. Initial treatment often leaves residual disease, from which the tumour regrows. Eventually, most tumours become resistant to all available chemotherapy. I call this pan-resistance to distinguish it from multi-drug resistance, usually describing resistance caused by upregulation of drug transporters, such as P-glycoprotein. In this review, I discuss mechanisms proposed to explain both residual disease and pan-resistance. Although plausible explanations are at hand for residual disease, pan-resistance is still a mystery. My conclusion is that it is time for a major effort to solve this mystery using the new genetically modified mouse tumour models that produce real tumours resembling cancer in human patients.

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