Abstract
Colorectal cancer is the third most common malignancy worldwide. 5-fluorouracil (5-FU) is the commonly used chemotherapeutic agent, however, more patients develop resistance. Phosphatidylinositol 3-kinases (PI3Ks) play a crucial role in a wide range of cellular processes associated with malignant behavior including cell growth, migration, and survival. In this study, we show increased expression of PI3K p85α during the progression of colorectal cancer. Silencing of PI3K p85α in colorectal cancer cells increased disruption of mitochondrial membrane potential and enhanced 5-FU-induced apoptosis. Furthermore, PI3K p85α-depletion results in activated expression of apoptosis-associated genes Bcl-6, Bim, and Bax. Our results suggest that knockdown of PI3K p85α is a potential therapeutic strategy in the treatment of colorectal cancer.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects*
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Apoptosis / genetics*
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Apoptosis Regulatory Proteins / genetics
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Bcl-2-Like Protein 11
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Colorectal Neoplasms / drug therapy*
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Colorectal Neoplasms / genetics
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Colorectal Neoplasms / pathology
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DNA-Binding Proteins / genetics
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Disease Progression
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Female
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Fluorouracil / pharmacology*
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Gene Silencing
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Humans
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Male
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Membrane Potential, Mitochondrial / drug effects
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Membrane Potential, Mitochondrial / genetics
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Membrane Proteins / genetics
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Middle Aged
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Phosphatidylinositol 3-Kinases / genetics*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins c-bcl-6
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bcl-2-Associated X Protein / genetics
Substances
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Apoptosis Regulatory Proteins
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BAX protein, human
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BCL2L11 protein, human
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BCL6 protein, human
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Bcl-2-Like Protein 11
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DNA-Binding Proteins
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Membrane Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-6
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bcl-2-Associated X Protein
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Phosphatidylinositol 3-Kinases
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Fluorouracil