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[Effect of LDHA Knockdown by siRNA on Migration and Invasion of ErbB2 Overexpressing Breast Cancer Cell Line]

Li He1,2, Meng-Long Li2, Yue Shen3

  • 1Department of Microbiology and Biochemical Pharmacy, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.

Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition
|May 1, 2019
PubMed
Abstract

Insights

Small interfering RNA targeting lactate dehydrogenase A (siLDHA) effectively inhibited breast cancer cell migration and invasion. This was achieved by downregulating glycolysis, offering a potential therapeutic strategy for ErbB2-overexpressing cancers.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Epidermal growth factor receptor 2 (ErbB2) overexpression is common in aggressive breast cancers.
  • Lactate dehydrogenase A (LDHA) plays a role in cancer cell metabolism and proliferation.
  • Targeting metabolic pathways is a promising strategy in cancer therapy.

Purpose of the Study:

  • To investigate the impact of siLDHA on migration and invasion in ErbB2-overexpressing breast cancer cells (SK-BR-3, MDA-MB-453).
  • To elucidate the molecular mechanisms underlying these effects, focusing on glycolysis.

Main Methods:

  • Transfection of SK-BR-3 and MDA-MB-453 cells with siLDHA.
  • Western blot analysis to confirm LDHA protein downregulation.
  • Transwell assays to assess cell migration and invasion.
  • Measurement of lactate dehydrogenase (LDH) activity, glucose uptake, and lactate production.

Main Results:

  • siLDHA significantly reduced LDHA protein levels in both cell lines.
  • siLDHA markedly decreased migration and invasion capabilities of SK-BR-3 and MDA-MB-453 cells.
  • siLDHA lowered LDH activity, glucose uptake, and lactate production, indicating glycolysis inhibition.

Conclusions:

  • Knockdown of LDHA inhibits migration and invasion in ErbB2-overexpressing breast cancer cells.
  • The mechanism involves the downregulation of glycolysis.
  • siLDHA represents a potential therapeutic target for ErbB2-positive breast cancers.
Keywords:
Breast cancerGlycolysisLactate dehydrogenase AMigration and invasionsiRNA

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