Downregulation of GLUT3 Promotes Apoptosis and Chemosensitivity of Acute Myeloid Leukemia Cells via EGFR Signaling.

Abstract

BACKGROUND:

Glucose transporter 3 (GLUT3) plays an important role in tumor progression and drug resistance in numerous malignancies, including acute myeloid leukemia (AML). However, the effect of GLUT3 silencing on treatment of AML remains poorly understood. The purpose of this study was to investigate role of GLUT3 in proliferation and chemosensitivity of AML and its underlying mechanisms.

METHODS:

The siRNA transfection was conducted using LipofectamineTM 2000. Quantitative real-time RT-PCR (qRT-PCR) and Western blot analyses were employed to measure the expression levels of mRNA and protein for GLUT3, respectively. The cytotoxic effects of siRNA and vincristine were determined using the MTT assay. Flow cytometry was performed to analyze apoptosis.

RESULTS:

GLUT3 siRNA transfection significantly reduced expression levels of GLUT3 mRNA and protein, leading to a strong growth inhibition and enhanced apoptosis (P = 0.017) in AML cells. Moreover, treatment with GLUT3 siRNA, synergistically enhanced the cytotoxic and apoptotic effects of vincristine (P = 0.025). We further investigated the possible mechanism involved in regulation of GLUT3 in AML cell proliferation and apoptosis. We found that GLUT3 negatively regulates EGFR activity, as well as the expression of its downstream proteins.

CONCLUSION:

Our results demonstrated that GLUT3 plays a fundamental role in the survival and resistance of AML cells to vincristine. Therefore, GLUT3 can be considered as an attractive target for gene therapy of AML patients and siRNA-mediated silencing of this gene may be a novel strategy in AML treatment.

• Authors: Yan Zhuang, Jing Zhao, Xi Xu, Laixi Bi
• Journal: Archives of Iranian medicine (Arch Iran Med) Vol. 21 Issue 2 Pg. 73-78 (02 01 2018) ISSN: 1735-3947 [Electronic] Iran
• PMID: 29664658 (Publication Type: Journal Article)
• Copyright: © 2018 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Chemical References

• Glucose Transporter Type 3
• RNA, Messenger
• RNA, Small Interfering
• SLC2A3 protein, human
• Vincristine
• ErbB Receptors

Topics

• Apoptosis
• Cell Proliferation
• Cell Survival
• Down-Regulation
• Drug Synergism
• ErbB Receptors (genetics, metabolism)
• Flow Cytometry
• Glucose Transporter Type 3 (genetics)
• Humans
• Leukemia, Myeloid, Acute (genetics, pathology)
• RNA, Messenger (genetics, metabolism)
• RNA, Small Interfering (genetics)
• Signal Transduction
• THP-1 Cells
• Transfection
• U937 Cells
• Vincristine (pharmacology)