Related Experiment Video

Updated: Mar 17, 2026

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

7.7K

Selective GPR55 antagonism reduces chemoresistance in cancer cells

Nagendra S Singh1, Michel Bernier2, Irving W Wainer3

  • 1Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health (NIH), Baltimore, MD 21224, USA.

Pharmacological Research
|July 18, 2016
PubMed

Insights

The G protein-coupled receptor 55 (GPR55) antagonist MNF shows anti-tumor effects by reducing cancer biomarkers and multidrug resistance proteins. MNF also enhances the efficacy of chemotherapy drugs like doxorubicin and gemcitabine.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • G protein-coupled receptor 55 (GPR55) is implicated in cancer progression.
  • Multidrug resistance (MDR) proteins like P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) limit chemotherapy effectiveness.
  • The GPR55 antagonist (R,R')-4'-methoxy-1-naphthylfenoterol (MNF) may offer a therapeutic strategy.

Purpose of the Study:

  • To investigate the anti-tumorigenic effects of MNF in pancreatic cancer cells (PANC-1).
  • To examine MNF's impact on cancer biomarkers and MDR protein expression and function.
  • To assess MNF's potential to enhance chemotherapy efficacy.

Main Methods:

  • PANC-1 cells were treated with MNF, and levels of EGF receptor, pyruvate kinase M2 (PKM2), β-catenin, HIF-1α, Pgp, and BCRP were analyzed.
  • GPR55 inhibition was achieved using MNF or CID 16020046.
  • Doxorubicin accumulation and cytotoxicity of doxorubicin and gemcitabine in MNF-treated cells were evaluated.
  • Similar experiments were conducted in MDA-MB-231 and U87MG cell lines.

Main Results:

  • MNF treatment reduced EGF receptor, PKM2, β-catenin, and nuclear HIF-1α levels.
  • GPR55 inhibition decreased total and nuclear Pgp and BCRP expression.
  • MNF treatment led to doxorubicin nuclear accumulation and enhanced the cytotoxicity of doxorubicin and gemcitabine.
  • These effects were also observed in other cancer cell lines expressing GPR55.

Conclusions:

  • GPR55 inhibition by MNF exhibits anti-tumor activity by downregulating key cancer biomarkers and MDR proteins.
  • MNF potentiates chemotherapy by overcoming multidrug resistance, suggesting a potential therapeutic approach for various cancers.
  • The findings implicate the MEK/ERK and PI3K-AKT pathways in GPR55-mediated regulation of MDR proteins.
Keywords:
Cancer biomarkersGPR55Hypoxia-inducible factor 1α (HIF-1α)Multidrug resistance (MDR)Pyruvate kinase M2 (PKM2)β-Catenin

More Related Videos

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo09:19

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo

Published on: February 6, 2015

9.2K
Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel06:44

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel

Published on: September 8, 2017

14.1K

Related Concept Videos

Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.9K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
9.1K
G Protein-coupled Receptors01:15

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
19.0K
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates...
723
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
8.6K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
63