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Title: Inhibition of PKM2 sensitizes triple-negative breast cancer cells to doxorubicin

Highlights: • Suppression of PKM2 sensitizes triple-negative breast cancer cells to doxorubicin. • Repression of PKM2 affects the glycolysis and decreases ATP production. • Downregulation of PKM2 increases the intracellular accumulation of doxorubicin. • Inhibition of PKM2 enhances the antitumor efficacy of doxorubicin in vivo. - Abstract: Cancer cells alter regular metabolic pathways in order to sustain rapid proliferation. One example of metabolic remodeling in cancerous tissue is the upregulation of pyruvate kinase isoenzyme M2 (PKM2), which is involved in aerobic glycolysis. Indeed, PKM2 has previously been identified as a tumor biomarker and as a potential target for cancer therapy. Here, we examined the effects of combined treatment with doxorubicin and anti-PKM2 small interfering RNA (siRNA) on triple-negative breast cancer (TNBC). The suppression of PKM2 resulted in changes in glucose metabolism, leading to decreased synthesis of adenosine triphosphate (ATP). Reduced levels of ATP resulted in the intracellular accumulation of doxorubicin, consequently enhancing the therapeutic efficacy of this drug in several triple-negative breast cancer cell lines. Furthermore, the combined effect of PKM2 siRNA and doxorubicin was evaluated in an in vivo MDA-MB-231 orthotopic breast cancer model. The siRNA was systemically administered through a polyethylenimine (PEI)-based delivery system that has been extensivelymore » used. We demonstrate that the combination treatment showed superior anticancer efficacy as compared to doxorubicin alone. These findings suggest that targeting PKM2 can increase the efficacy of chemotherapy, potentially providing a new approach for improving the outcome of chemotherapy in patients with TNBC.« less
Authors:
 [1] ;  [2] ;  [3] ;  [2]
  1. Department of Gastroenterology, The Tenth People’s Hospital of Shanghai, Tongji University, Shanghai 200072 (China)
  2. (United States)
  3. Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030 (United States)
Publication Date:
OSTI Identifier:
22416839
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 454; Journal Issue: 3; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; ATP; BIOLOGICAL MARKERS; BIOLOGICAL PATHWAYS; CELL PROLIFERATION; CHEMOTHERAPY; DOXORUBICIN; GLUCOSE; GLYCOLYSIS; IN VIVO; INHIBITION; MAMMARY GLANDS; NEOPLASMS; PATIENTS; RNA; SYNTHESIS