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Published on: October 28, 2014
Gene expression profile in colon cancer cells with respect to XIAP expression status
Liang Qiao1, Gloria H Y Li, Yun Dai
1Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China.
Background And Aims:
We observed a marked synergism between peroxisome proliferator-activated receptor gamma (PPARgamma) ligands and X-linked inhibitor of apoptosis (XIAP) down-regulation in colon cancer. In the current study, we detected the gene expression profile in HCT116 cells treated with or without PPARgamma ligand troglitazone.
Materials And Methods:
HCT116-XIAP(+/+) and HCT116-XIAP(-/-) cells were treated with or without 50 microM troglitazone for 48 h. Gene expressions were detected by microarray, and selected genes were validated by reverse-transcriptase polymerase chain reaction (PCR), real-time PCR, and Western blot.
Results:
Relative to HCT116-XIAP(+/+) cells, 58 genes were up-regulated and 33 genes down-regulated in HCT116-XIAP(-/-) cells, all by > or =4-fold. These genes could be classified into a wide variety of functional classes, but we focused on those related to angiogenesis, apoptosis, and proliferation. Thus, two pro-apoptotic genes and one pro-proliferation gene were up-regulated in HCT116-XIAP(-/-) cells. Two pro-proliferation genes, one pro-angiogenesis gene, one anti-angiogenesis gene, and one anti-apoptosis gene were down-regulated in HCT116-XIAP(-/-) cells. Relative to HCT116-XIAP(+/+) cells treated with troglitazone, 137 genes were up-regulated, and 31 genes were down-regulated in troglitazone-treated HCT116-XIAP(-/-) cells, all by > or =4-fold. Among the up-regulated genes were two anti-angiogenesis genes, seven pro-apoptosis genes, and six anti-proliferation genes. Among the down-regulated genes were one anti-angiogenesis gene, one pro-angiogenesis gene, one anti-apoptosis gene, one anti-proliferation gene, and two pro-proliferation genes.
Conclusion:
Down-regulation of XIAP in HCT116 cells with or without troglitazone treatment was associated with changes of gene expression that favor increased tendency of apoptosis, decreased cell proliferation, and angiogenesis potential.
Insights
Down-regulating X-linked inhibitor of apoptosis (XIAP) in colon cancer cells synergizes with peroxisome proliferator-activated receptor gamma (PPARgamma) ligands. This gene expression shift promotes apoptosis and reduces proliferation and angiogenesis.
Area of Science:
- Molecular Biology
- Cancer Research
- Genomics
Background:
- A significant synergy exists between peroxisome proliferator-activated receptor gamma (PPARgamma) ligands and X-linked inhibitor of apoptosis (XIAP) down-regulation in colon cancer.
- This study investigates the gene expression profile of HCT116 cells treated with or without the PPARgamma ligand troglitazone.
Purpose of the Study:
- To analyze the gene expression profile in HCT116 colon cancer cells with and without XIAP down-regulation, in the presence or absence of troglitazone.
- To identify key genes and pathways affected by the combined treatment, focusing on apoptosis, proliferation, and angiogenesis.
Main Methods:
- HCT116 cells with and without XIAP (HCT116-XIAP(+/+) and HCT116-XIAP(-/-)) were treated with troglitazone (50 microM) for 48 hours.
- Gene expression was analyzed using microarray, with validation through reverse-transcriptase polymerase chain reaction (PCR), real-time PCR, and Western blot.
Main Results:
- XIAP down-regulation in HCT116 cells altered the expression of 91 genes, including pro-apoptotic and pro-proliferation genes.
- Troglitazone treatment in XIAP-down-regulated cells resulted in significant changes in 168 genes, including anti-angiogenesis, pro-apoptosis, and anti-proliferation genes.
- Specific gene changes indicate a shift towards increased apoptosis, reduced proliferation, and altered angiogenesis potential.
Conclusions:
- XIAP down-regulation in HCT116 cells, with or without troglitazone, is linked to gene expression changes favoring apoptosis.
- The observed gene expression alterations suggest a decreased potential for cell proliferation and angiogenesis.
- These findings highlight a potential therapeutic strategy combining XIAP targeting with PPARgamma agonists in colon cancer treatment.
