Related Experiment Video

Updated: Sep 7, 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

Resistin induces multidrug resistance in myeloma by inhibiting cell death and upregulating ABC transporter expression

Jianan Pang1,2, Qiaofa Shi2,3, Zhiqiang Liu2

  • 1Cancer Center, The First Hospital of Jilin University, Changchun, Jilin Province, China.

Haematologica
|April 1, 2017
PubMed

Insights

Resistin, an adipokine, protects multiple myeloma cells from chemotherapy-induced apoptosis by inhibiting caspase cleavage and increasing drug efflux. Targeting resistin may overcome drug resistance in multiple myeloma patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Multiple myeloma is an incurable blood cancer with frequent relapse, necessitating identification of drug resistance factors.
  • Bone marrow adipocytes and their secreted adipokines are implicated in chemotherapy resistance, but mechanisms remain unclear.

Purpose of the Study:

  • To investigate the role of resistin, an adipokine, in mediating chemotherapy resistance in multiple myeloma.
  • To elucidate the molecular mechanisms by which resistin confers drug resistance.

Main Methods:

  • Assessed resistin's effect on chemotherapy-induced apoptosis in myeloma cell lines and primary samples.
  • Investigated resistin's impact on caspase cleavage, NF-κB and PI3K/Akt pathways.
  • Examined resistin's influence on ATP-binding cassette (ABC) transporter expression and function via DNA methyltransferases (DNMTs).
  • Validated findings in in vivo preclinical models.

Main Results:

  • Resistin significantly abrogated chemotherapy-induced apoptosis in multiple myeloma cells.
  • Resistin inhibited caspase cleavage through NF-κB and PI3K/Akt signaling pathways.
  • Resistin decreased DNMT1 and DNMT3a expression, reducing ABC transporter gene promoter methylation and enhancing drug efflux.
  • In vivo studies confirmed resistin's protective role against chemotherapy-induced apoptosis.

Conclusions:

  • Resistin plays a novel role in multiple myeloma pathogenesis by promoting chemotherapy resistance.
  • Targeting resistin presents a potential therapeutic strategy to overcome multidrug resistance in multiple myeloma.

More Related Videos

Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics12:28

Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics

Published on: January 11, 2019

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype14:51

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype

Published on: June 17, 2022

Related Concept Videos

ABC Transporters: Exporter01:31

ABC Transporters: Exporter

ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
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 specific...
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...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Carrier-Mediated Transport01:06

Carrier-Mediated Transport

Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...