Abstract
Hypoxia has been proved to be a typical character of solid tumors. Tumor cells prefer to use glucose through the glycolysis pathway instead of aerobic respiration. However, the precise molecular mechanism underlying this so-called Warburg effect remains elusive. In the current study, siRNA was synthesized and transfected into BxPC-3 cell line to silence the expression of HIF-1α gene. It was found that hypoxia induced hypoxia-inducible factor 1α (HIF-1α) overexpression in BxPC-3 cells, enhanced the expression of pyruvate dehydrogenase kinase 1 and lactate dehydrogenase A, thus facilitating glycolysis and making tumor cells more tolerant to hypoxic stress. The silencing of HIF-1α gene significantly attenuated glycolysis under hypoxic conditions, inhibited the growth and invasion ability of BxPC-3 cells, and enhanced hypoxia-induced cell apoptosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis
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Cell Hypoxia
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Cell Line, Tumor
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Cell Proliferation
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Female
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Gene Expression / drug effects
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Gene Silencing*
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Glycolysis / genetics*
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
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Hypoxia-Inducible Factor 1, alpha Subunit / physiology*
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Isoenzymes / genetics
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L-Lactate Dehydrogenase / genetics
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Lactate Dehydrogenase 5
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Lactic Acid / biosynthesis
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Mice
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Mice, Nude
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Neoplasm Invasiveness
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Neoplasm Transplantation
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Pancreatic Neoplasms / genetics*
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Pancreatic Neoplasms / pathology*
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Protein Serine-Threonine Kinases / genetics
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Pyruvate Dehydrogenase Acetyl-Transferring Kinase
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RNA, Small Interfering / genetics
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Transfection
Substances
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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Isoenzymes
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Pyruvate Dehydrogenase Acetyl-Transferring Kinase
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RNA, Small Interfering
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Lactic Acid
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L-Lactate Dehydrogenase
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Lactate Dehydrogenase 5
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Protein Serine-Threonine Kinases