Related Experiment Video

Updated: Apr 16, 2026

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
07:02

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice

Published on: August 23, 2019

7.9K

Iodide- and glucose-handling gene expression regulated by sorafenib or cabozantinib in papillary thyroid cancer

Maomei Ruan1, Min Liu, Qianggang Dong

  • 1Department of Nuclear Medicine (M.R., M.L., L.C.), Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China; and Section of Cancer Stem Cells (Q.D.), Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai 200032, China.

The Journal of Clinical Endocrinology and Metabolism
|March 14, 2015
PubMed
Abstract

Insights

Tyrosine kinase inhibitors sorafenib and cabozantinib can restore iodide-handling gene expression and inhibit glucose metabolism in papillary thyroid cancer (PTC) cells. This suggests potential for improved radioiodine therapy in PTC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Papillary thyroid cancer (PTC) often exhibits silenced iodide-handling genes and increased glucose metabolism, hindering radioiodine treatment effectiveness.
  • The RET/PTC1 rearrangement is a common genetic alteration in PTC, contributing to aberrant gene expression patterns.

Purpose of the Study:

  • To investigate the impact of tyrosine kinase inhibitors (TKIs) sorafenib and cabozantinib on iodide-handling and glucose-handling gene expression in PTC cells with RET/PTC1 rearrangement.
  • To evaluate the effects of these TKIs on cell proliferation, cell cycle, apoptosis, and key signal transduction pathways.

Main Methods:

  • In vitro study using BHP 2-7 cells harboring RET/PTC1 rearrangement.
  • Assessed cell proliferation, cell cycle, and apoptosis using standard assays.
  • Utilized Western blot to analyze signal transduction pathways.
  • Employed quantitative real-time PCR, Western blot, immunofluorescence, and radioisotope uptake assays to evaluate gene expression and iodide uptake.

Main Results:

  • Both sorafenib and cabozantinib inhibited PTC cell proliferation and induced G0/G1 cell cycle arrest.
  • Sorafenib and cabozantinib modulated key signaling pathways, including RET, AKT, and ERK1/2.
  • Treatment with either TKI restored iodide-handling gene expression and enhanced radioiodine uptake.
  • Both drugs significantly decreased glucose transporter gene expression and (18)F-fluorodeoxyglucose accumulation.

Conclusions:

  • Sorafenib and cabozantinib demonstrate significant anti-proliferative effects and modulate signaling in PTC cells with RET/PTC1 rearrangement.
  • These TKIs show potential for enhancing iodide-handling gene expression and inhibiting glucose metabolism.
  • The findings suggest that sorafenib and cabozantinib could be valuable in improving radioiodine treatment strategies for papillary thyroid cancer.

More Related Videos

Radionuclide-fluorescence Reporter Gene Imaging to Track Tumor Progression in Rodent Tumor Models10:04

Radionuclide-fluorescence Reporter Gene Imaging to Track Tumor Progression in Rodent Tumor Models

Published on: March 13, 2018

12.7K
Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down08:59

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

Related Concept Videos

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...
71
Synthesis and Regulation of Thyroid Hormones01:20

Synthesis and Regulation of Thyroid Hormones

Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
9.4K
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...
9.2K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.2K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.1K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
5.0K