Peroxisome proliferator-activated receptor-γ activation inhibits tumor progression in non-small-cell lung cancer

Keshamouni, Venkateshwar G.; Reddy, Raju C.; Joel, Binju; Thannickal, Victor J.; Kalemkerian, Gregory P.; Standiford, Theodore J.

doi:10.1038/sj.onc.1206885

Cited by 189 publications

(200 citation statements)

References 44 publications

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“…Rosiglitazone has been tested on various cancers including colon cancer [14][15][16][17][18][19][20] with wide effective dose ranges. However, the anticancer effect of rosiglitazone varies considerably in different cancers, and even in the same cancer type, the reported results are variable.…”

mentioning

confidence: 99%

Loss of XIAP sensitizes rosiglitazone‐induced growth inhibition of colon cancer in vivo

Dai

Qiao

Chan

et al. 2008

Intl Journal of Cancer

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Ligands for peroxisome proliferator-activated receptor gamma (PPARc) possess anticancer properties. However, the efficacy of PPARc ligands varies in different cancers. In colon cancer, the role of PPARc and its ligands is controversial. We recently showed that downregulation of X-linked inhibitor of apoptosis protein (XIAP) could sensitize colon cancer cells to troglitazone, and 15-deoxy-D12,14-prostaglandin J2 (15-PGJ2) induced cell killing. In our study, we aimed to examine whether rosiglitazone, another more clinically relevant PPARc ligand, has any synergistic anticancer effect with XIAP downregulation in colon cancer. Human colon cancer cell lines HCT116-XIAP 1/1 cells and HCT116-XIAP 2/2 cells were treated with various concentrations of rosiglitazone. The effects of rosiglitazone on cell proliferation, apoptosis and growth of xenograft colon cancers were studied. Rosiglitazone barely suppressed the growth and only very weakly induced apoptosis in HCT116 cells in vitro. Loss of XIAP did not sensitize HCT116 cells to rosiglitazone-induced growth inhibition or apoptosis. In vivo studies revealed that rosiglitazone strongly suppressed the growth of xenograft colon cancer, especially tumors derived from HCT116-XIAP 2/2 cells. The rosiglitazone-treated tumor had reduced expression of ki-67 and lowered mitotic rate. Downregulation of XIAP was associated with an impaired activation of PPARc by its ligand. Rosiglitazone induced marked upregulation of PTEN in HCT116-XIAP 2/2 cells, as well as in xenograft tumors derived from HCT116-XIAP 2/2 cells. We concluded that rosiglitazone significantly suppresses the growth of xenograft colon cancer, and downregulation of XIAP sensitizes the xenograft tumors to rosiglitazone-induced tumor suppression in vivo via upregulation of PTEN.

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mentioning

confidence: 99%

Loss of XIAP sensitizes rosiglitazone‐induced growth inhibition of colon cancer in vivo

Dai

Qiao

Chan

et al. 2008

Intl Journal of Cancer

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“…12 As stated above, PPARg ligands inhibit stimulusmediated COX-2 expression in airway epithelial cells. 44 Inhibiting COX-2 also inhibits angiogenesis and carcinogenesis.…”

Section: Lung Cancermentioning

confidence: 93%

“…64 Moreover, PPARg is strikingly upregulated upon differentiation of monocytes to macrophages, 7 and is elevated in asthma 65,66 and in cancer cells. 12 In contrast to other tissues, however, PPARg is downregulated in adipose tissue by proinflammatory cytokines (TNF-a, IL-1b, and IL-6), 7 indicating that, like PPARa, regulation of PPARg expression can be cell typespecific. PPARg is also downregulated by IFN-g and LPS in macrophages, 45 and by steroids in the lung.…”

Section: Transcriptional Regulation Of Ppar Expressionmentioning

confidence: 99%

“…12,24,44,[102][103][104][105][106] For example, in addition to modulating inflammation, there is growing evidence that NSAIDs (e.g., sulindac sulfide and indomethacin), as well as TZDs, may promote epithelial-cell differentiation by activating PPARg. 12,103 This was observed in vitro and in animal tumor models 107 for both nonsmall-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) lines. The overexpression of PPARg in these models also inhibited tumor growth.…”

Section: Lung Cancermentioning

confidence: 99%

“…Following their identification, a rapidly increasing number of articles and reviews have been written, including those that focus on PPAR expression, function, and regulation, 2,3 as well as their role in lipid and glucose metabolism, [4][5][6][7] diabetes and obesity, [8][9][10] atherosclerosis, 4,8,11 cellular proliferation/differentiation, [12][13][14][15] neurological diseases, [16][17][18] and inflammation/immunity. 7,[19][20][21] These publications are recommended to readers who want additional information on these topics.…”

Section: Introductionmentioning

confidence: 99%

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Peroxisome Proliferator‐Activated Receptors: Potential Therapeutic Targets in Lung Disease?

Denning

Stoll

2005

Pediatric Pulmonology

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The peroxisome proliferator‐activated receptors (PPARs) are a family of nuclear hormone receptors that play central roles in lipid and glucose homeostasis, cellular differentiation, and the immune/inflammatory response. Growing evidence indicates that changes in expression and activation of PPARs likely modulate conditions as diverse as diabetes, atherosclerosis, cancer, asthma, Parkinson's disease, and Alzheimer's disease. Activation of these receptors by natural or pharmacologic ligands leads to both gene‐dependent and gene‐independent effects that alter the expression of a wide array of proteins. In the lung, PPARs are expressed by alveolar macrophages, as well as by epithelial, endothelial, and smooth muscle cells. Studies both in vitro and in vivo suggest that PPAR ligands may have anti‐inflammatory effects in asthma, pulmonary sarcoidosis, and pulmonary alveolar proteinosis, as well as antiproliferative and antiangiogenic effects in epithelial lung cancers. Further studies to understand the contribution of these receptors to health and disease will be important for determining whether they represent a promising target for therapeutic intervention. Pediatr Pulmonol. © 2005 Wiley‐Liss, Inc.

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ADAR1 is a prognostic biomarker and is correlated with immune infiltration in lung adenocarcinoma

Yang

Chen

et al. 2023

Cancer Medicine

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Background: Lung adenocarcinoma (LUAD) is a common subtype of non-small cell lung cancer with high morbidity and mortality rates and is usually detected at advanced stages because of the early onset of metastasis. Adenosine deaminase RNA-specific 1 (ADAR1) is an RNA editing enzyme that catalyzes the important physiological process of adenosine-to-inosine editing and has been shown to participate in the progression of LUAD. Increasing evidence has suggested that immune infiltration of the tumor immune microenvironment has prognostic value for most human solid organ malignancies; however, much is unknown about the functions of ADAR1. Methods:The expression of ADAR1 was analyzed in The Cancer Genome Atlas -LUAD database and validated in our LUAD cohort. To assess the prognostic value of ADAR1, Kaplan-Meier survival analyses and Cox regression analyses were carried out in LUAD cohorts. The association between ADAR1 and LUAD immune infiltrates via analyses of cell-type identification by estimating relative subsets of known RNA transcripts. Furthermore, multiplex immunohistochemistry was used to confirm the relationship between ADAR1 expression and immune cells in the present cohort of patients with LUAD.Results: ADAR1 was highly expressed in LUAD tissues and closely correlated with lymph node metastasis (LNM) (p < 0.01), advanced tumor stage (p < 0.05), and poor patient prognosis (p < 0.01), thus indicating that increased ADAR1 contributed to the progression of LUAD. LUAD with high ADAR1 expression can metastasize to lymph nodes that express more ADAR1 than the primary lesion.In addition, M0 macrophages and M2 macrophages increased and CD4 + T cells decreased in LUAD tissues with high ADAR1 expression. And the expression of ADAR1 in lymph node metastases was negatively correlated with the contents of CD4 + T cells (p = 0.0017) and M1 macrophages (p = 0.0037). Conclusion:The findings of our study suggested that ADAR1 may be useful in predicting prognosis and LNM in LUAD, and may serve as a promising immunerelated molecular target for LUAD patients.

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Peroxisome proliferator-activated receptor-γ activation inhibits tumor progression in non-small-cell lung cancer

Cited by 189 publications

References 44 publications

Loss of XIAP sensitizes rosiglitazone‐induced growth inhibition of colon cancer in vivo

Loss of XIAP sensitizes rosiglitazone‐induced growth inhibition of colon cancer in vivo

Peroxisome Proliferator‐Activated Receptors: Potential Therapeutic Targets in Lung Disease?

ADAR1 is a prognostic biomarker and is correlated with immune infiltration in lung adenocarcinoma

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