Suppression of pancreatic carcinoma growth by activating peroxisome proliferator-activated receptor γ involves angiogenesis inhibition

Ye, Dong; Wang, Xingpeng; Wu, Kai

doi:10.3748/wjg.15.441

Cited by 45 publications

(30 citation statements)

References 18 publications

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“…In this context, antimetastatic but not anti-proliferative effects were also reported after treatment of pancreas cancer with a synthetic PPAR-ligand (T0070907), known to be a specific PPARantagonist (Nakajima et al, 2008). In contrast, PPAR-agonists were shown to inhibit the growth of pancreas tumours via downregulation of VEGF and thus inhibition of tumour angiogenesis (Dong et al, 2009). This is in line with previous observations suggesting an involvement of PPAR-signalling in the angiogenesis process (Panigrahy et al 2002).…”

Section: Influence Of Ppar On Pancreas Metastasissupporting

confidence: 79%

Pancreatic Cancer: Current Concepts in Invasion and Metastasis

Chiblak¹,

Abdollahi²

2012

Pancreatic Cancer - Molecular Mechanism and Targets

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Section: Influence Of Ppar On Pancreas Metastasissupporting

confidence: 79%

Pancreatic Cancer: Current Concepts in Invasion and Metastasis

Chiblak¹,

Abdollahi²

2012

Pancreatic Cancer - Molecular Mechanism and Targets

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“…PPAR-c is a nuclear receptor serving as a transcription factor to control cell differentiation, apoptosis and glucose metabolism (Kliewer and Wilson 1998). Ligands for PPAR-c such as anti-diabetic drugs of the thiazolidinedione (TDD) class pioglitazone, troglitazone and rosiglitazone (Cho and Momose 2008;Krentz et al 2008) exert anti-inflammatory effects and reduce PC growth in experimental models (Nakajima et al 2008;Dong et al 2009). The antiinflammatory effects associate with suppression of COX-2 and NF-jB activities, evidencing complex intracellular pathways and their suppression of tumor growth partially occurs via reducing VEGF (Dong et al 2009).…”

Section: Ppar-c Ligands: General and Pancreas Cancer-specific Anti-tumentioning

confidence: 99%

“…Ligands for PPAR-c such as anti-diabetic drugs of the thiazolidinedione (TDD) class pioglitazone, troglitazone and rosiglitazone (Cho and Momose 2008;Krentz et al 2008) exert anti-inflammatory effects and reduce PC growth in experimental models (Nakajima et al 2008;Dong et al 2009). The antiinflammatory effects associate with suppression of COX-2 and NF-jB activities, evidencing complex intracellular pathways and their suppression of tumor growth partially occurs via reducing VEGF (Dong et al 2009). The expression of PPAR-c in human PC and the effects of its ligands on cell growth were studied (Sasaki et al 2001).…”

Section: Ppar-c Ligands: General and Pancreas Cancer-specific Anti-tumentioning

confidence: 99%

A Metabolic Inhibitory Cocktail for Grave Cancers: Metformin, Pioglitazone and Lithium Combination in Treatment of Pancreatic Cancer and Glioblastoma Multiforme

Elmacı

Altinöz²

2016

Biochem Genet

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Pancreatic cancer (PC) and glioblastoma multiforme (GBM) are among the human cancers with worst prognosis which require an urgent need for efficient therapies. Here, we propose to apply to treat both malignancies with a triple combination of drugs, which are already in use for different indications. Recent studies demonstrated a considerable link between risk of PC and diabetes. In experimental models, anti-diabetogenic agents suppress growth of PC, including metformin (M), pioglitazone (P) and lithium (L). L is used in psychiatric practice, yet also bears anti-diabetic potential and selectively inhibits glycogen synthase kinase-3 beta (GSK-3β). M, a biguanide class anti-diabetic agent shows anticancer activity via activating AMP-activated protein kinase (AMPK). Glitazones bind to PPAR-γ and inhibit NF-κB, triggering cell proliferation, apoptosis resistance and synthesis of inflammatory cytokines in cancer cells. Inhibition of inflammatory cytokines could simultaneously decrease tumor growth and alleviate cancer cachexia, having a major role in PC mortality. Furthermore, mutual synergistic interactions exist between PPAR-γ and GSK-3β, between AMPK and GSK-3β and between AMPK and PPAR-γ. In GBM, M blocks angiogenesis and migration in experimental models. Very noteworthy, among GBM patients with type 2 diabetes, usage of M significantly correlates with better survival while reverse is true for sulfonylureas. In experimental models, P synergies with ligands of RAR, RXR and statins in reducing growth of GBM. Further, usage of P was found to be lesser in anaplastic astrocytoma and GBM patients, indicating a protective effect of P against high-grade gliomas. L is accumulated in GBM cells faster and higher than in neuroblastoma cells, and its levels further increase with chronic exposure. Recent studies revealed anti-invasive potential of L in GBM cell lines. Here, we propose that a triple-agent regime including drugs already in clinical usage may provide a metabolic adjuvant therapy for PC and GBM.

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“…Thus, the level of proliferating cell nuclear antigen (PCNA), an established index for proliferation cells, was firstly assessed to determine cell proliferation in PANC-1 cells [14] . Western blot analysis clearly shows that PCNA protein expression undergoes a down-regulation change in a time-dependent manner after exposure to ASA (Figure 2A).…”

Section: Asa Decreases Proliferation Instead Of Inducing Apoptosis Ormentioning

confidence: 99%

Aspirin inhibits proliferation of gemcitabine-resistant human pancreatic cancer cells and augments gemcitabine-induced cytotoxicity

Zhu

et al. 2009

Acta Pharmacol Sin

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Aim: To investigate whether aspirin is able to augment gemcitabine-induced cytotoxicity in human pancreatic cancer cells. Methods: Two gemcitabine-insensitive human pancreatic cancer cell lines, PANC-1 and Capan-1, were used. Cells were treated with either aspirin or gemcitabine alone or both of them. Cell growth and apoptosis were determined by MTT assay, Annexin V or Hoechest 33258 staining. Cell cycle distribution was examined by flow cytometry. Western blot with specific phosphorylated protein antibodies was used to detect the activation of protein kinase. RT-PCR and Western blot were applied to assess the transcription and protein level for cyclin D1 and Bcl-2. Results: Aspirin alone significantly inhibits the proliferation of PANC-1 cells by causing cell cycle arrest at G 1 phase. Aspirin potentiates the anti-survival effect of gemcitabine as well as its pro-apoptotic effect in PANC-1 cells, although aspirin per se does not trigger apoptosis. Aspirin inhibits GSK-3β activation and suppresses the expression of its downstream gene products (cyclin D1 and Bcl-2), which are implicated in proliferation, survival and chemoresistance of pancreatic cancer. The effects of aspirin on Capan-1, were similar to that on PANC-1. Conclusion: Our results suggest that aspirin inhibits the proliferation of gemcitabine-resistant pancreatic cancer cells and augments the antisurvival effect of gemcitabine, probably by suppressing the activity of GSK-3β and its downstream gene products.

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Suppression of pancreatic carcinoma growth by activating peroxisome proliferator-activated receptor γ involves angiogenesis inhibition

Abstract: AIM:To study the possible actions and mechanisms of peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated transcription factor, in pancreatic carcinogenesis, especially in angiogenesis.

Cited by 45 publications

References 18 publications

Pancreatic Cancer: Current Concepts in Invasion and Metastasis

Pancreatic Cancer: Current Concepts in Invasion and Metastasis

A Metabolic Inhibitory Cocktail for Grave Cancers: Metformin, Pioglitazone and Lithium Combination in Treatment of Pancreatic Cancer and Glioblastoma Multiforme

Aspirin inhibits proliferation of gemcitabine-resistant human pancreatic cancer cells and augments gemcitabine-induced cytotoxicity

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