Metformin inhibits P‐glycoprotein expression via the NF‐κB pathway and CRE transcriptional activity through AMPK activation

  title={Metformin inhibits P‐glycoprotein expression via the NF‐$\kappa$B pathway and CRE transcriptional activity through AMPK activation},
  author={Hyung Gyun Kim and Tran Thi Hien and Eun Hee Han and Yong Pil Hwang and Jae Ho Choi and Keon Wook Kang and Kwang‐il Kwon and Bong-Hee Kim and Sang Kyum Kim and Gye Yong Song and Tae Cheon Jeong and Hye Gwang Jeong},
  journal={British Journal of Pharmacology},
BACKGROUND AND PURPOSE The expression of P‐glycoprotein (P‐gp), encoded by the multidrug resistance 1 (MDR1) gene, is associated with the emergence of the MDR phenotype in cancer cells. We investigated whether metformin (1,1‐dimethylbiguanide hydrochloride) down‐regulates MDR1 expression in MCF‐7/adriamycin (MCF‐7/adr) cells. 

Reversal of multidrug resistance of hepatocellular carcinoma cells by metformin through inhibiting NF-κB gene transcription.

The synergistic effect of metformin and NF-κB siRNA were found in HepG2/ADM cells with regard to proliferation inhibition, cell cycle arrest and inducing cell apoptosis.

Metformin suppresses the proliferation and invasion through NF-kB and MMPs in MCF-7 cell line

Metformin may act on the proliferation, and the processes of invasion and metastasis of MCF-7 cells through blocking NF-kB, which is intensely expressed in breast cancer cells, and through diminishing the expression of M MP-2 and MMP-9 significantly.

Mechanism of P-glycoprotein expression in the SGC7901 human gastric adenocarcinoma cell line induced by cyclooxygenase-2.

  • K. GuYu Chen
  • Biology, Medicine
    Asian Pacific journal of cancer prevention : APJCP
  • 2012
COX-2 may induce the expression of P-gp in SGC7901 cell line via the NF-kappa B pathway with pacliaxel stimulation with dose- dependence.

Reversal of P-glycoprotein-mediated multidrug resistance is induced by mollugin in MCF-7/adriamycin cells.

Metformin increases the cytotoxicity of oxaliplatin in human DLD‐1 colorectal cancer cells through down‐regulating HMGB1 expression

Treatment with OXA and metformin resulted in cytotoxicity and cell growth inhibition synergistically, accompanied with reduced HMGB1 level, which may have implications for the rational design of future drug regimens incorporating OxA and meetformin for the treatment of CRC.

NF-κB decoy polyplexes decrease P-glycoprotein-mediated multidrug resistance in colorectal cancer cells

Modulate P-gp activity in colon cancer cells using NF-κB decoy oligodeoxynucleotides (ODNs) that are effectively delivered into the nucleus of colorectal cancer cells by self-assembling nonviral nanoparticles comprising the novel poly(N,N-dimethylaminoethylmethacrylate) diblock copolymer (pHPMA-b-pDMAEMA).

Metformin increases chemo-sensitivity via gene downregulation encoding DNA replication proteins in 5-Fu resistant colorectal cancer cells.

This study demonstrated metformin inhibited by cell proliferation, cell migration ability, clonogenic ability, and cancer stem cell population, and suggested novel anticancer mechanism of met formin that inhibited DNA replication machinery, such as the MCM family in SNU-C5_5FuR.



The MDR phenotype is associated with the expression of COX‐2 and iNOS in a human hepatocellular carcinoma cell line

The hypothesis that the MDR1 and angiogenic phenotypes are linked to each other in human liver cancer cell lines is supported.

NF-κB-mediated Induction of mdr1b Expression by Insulin in Rat Hepatoma Cells*

It is reported that the expression of ratmdr1b gene in cultured H-4-II-E hepatoma cells can be induced by insulin, and results suggest that the insulin-induced mdr1B expression is mediated by transcription factor NF-κB via the Raf-1 kinase signaling pathway.

Activation of β‐catenin signalling by GSK‐3 inhibition increases p‐glycoprotein expression in brain endothelial cells

Results suggest that regulation of p‐gp and other multidrug efflux transporters in brain vasculature can be influenced by β‐catenin signalling.

Regulation of MDR1 Expression and Drug Resistance by a Positive Feedback Loop Involving Hyaluronan, Phosphoinositide 3-Kinase, and ErbB2*♦

Data presented herein show that constitutive interaction of the pericellular polysaccharide, hyaluronan, with its receptor, CD44, regulates assembly and activation of an ErbB2-containing signaling complex, which in turn stimulates phosphoinositide 3-kinase activity in multidrug-resistant MCF-7/Adr human breast carcinoma cells.

Transcriptional Repression of Protein Kinase Cα via Sp1 by Wild Type p53 Is Involved in Inhibition of Multidrug Resistance 1 P-Glycoprotein Phosphorylation*

WT p53 may resensitize STS to chemotherapeutic agents by reducing MDR1 phosphorylation via transcriptional repression of PKCα expression, which indicates that molecular-based therapies targeting mutant p53 and PKC α may be an effective new strategy to improve chemotherAPEutic efficacy in STS.

Metformin Inhibits Cytokine-Induced Nuclear Factor &kgr;B Activation Via AMP-Activated Protein Kinase Activation in Vascular Endothelial Cells

It is suggested that metformin attenuates the cytokine-induced expression of proinflammatory and adhesion molecule genes by inhibiting NF-&kgr;B activation via AMPK activation, suggesting a possible role of AMPK in the regulation of cell inflammation.

Multiple physiological functions for multidrug transporter P-glycoprotein?

MDR1 genotype is associated with hepatic cytochrome P450 3A4 basal and induction phenotype

NF-k B-mediated Induction of mdr 1 b Expression by Insulin in Rat Hepatoma Cells

It is reported that the expression of rat mdr1b gene in cultured H-4-II-E hepatoma cells can be induced by insulin, and results suggest that the insulin-induced mDR1b expression is mediated by transcription factor NF-kB via the Raf-1 kinase signaling pathway.