Expression and Significance of Microsomal Prostaglandin Synthase-1 (mPGES-1) and Beclin-1 in the Development of Prostate Cancer

Xu, Luwei; Qian, Ming; Jia, Ru; Xu, Zheng; Wu, Jianping; Li, Wencheng; Huang, Wenbin; Chen, Xingguo

doi:10.7314/apjcp.2012.13.4.1639

Cited by 9 publications

(2 citation statements)

References 35 publications

(34 reference statements)

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“…BECN1 has therefore been identified as a candidate tumor suppressor gene for ovarian cancer (6). Previous studies have revealed that the expression of Beclin-1 is downregulated in breast (7), prostate (8) and nasopharyngeal (9) carcinomas. Further studies have revealed that a loss of Beclin-1 expression results in reduced autophagy activity and increased tumorigenesis (10).…”

Section: Introductionmentioning

confidence: 99%

Chemoresistance is associated with Beclin-1 and PTEN expression in epithelial ovarian cancers

Ying

Liu

et al. 2015

Oncology Letters

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The aim of the present study was to investigate the protein expression of the autophagy-related genes, BECN1 and PTEN, and the association with drug resistance in epithelial ovarian cancers. In total, 40 patients with pathologically diagnosed epithelial ovarian cancer were divided into a chemotherapy-sensitive group (n=20) and a chemotherapy-resistant group (n=20), according to the results of the pre- or post-operative normative chemotherapy and the post-operative follow-up. The protein expression of the phosphatase and tensin homolog (PTEN) and the BECN1 gene product, Beclin-1, was analyzed using immunohistochemistry in the 40 patients with ovarian carcinoma. The positive rate of Beclin-1 expression was significantly lower in the resistant group (35.0%) compared with the sensitive group (50.0%). The positive rate of PTEN expression was also significantly lower in the resistant group (30.0%) compared with the sensitive group (65.0%). Furthermore, the differences in the expression rates were revealed to be significant (P<0.05). The expression of Beclin-1 was identified to be positively correlated with the expression of PTEN (rs=0.816; P<0.0001). The low expression of the Beclin-1 and PTEN proteins in the ovarian cancer tissues was revealed to be closely associated with drug resistance. Therefore, Beclin-1 may interact with PTEN to participate in the mechanism of drug resistance and the changes in macrophage activity observed in cases of drug-resistant ovarian cancer.

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Section: Introductionmentioning

confidence: 99%

Chemoresistance is associated with Beclin-1 and PTEN expression in epithelial ovarian cancers

Ying

Liu

et al. 2015

Oncology Letters

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“…mPGES-1 is low in normal tissue and is induced in any inflammation. Studies have shown that it is overexpressed in a variety of human cancers, such as lung cancer [ 4 ], stomach cancer [ 5 ], colon cancer [ 6 ], prostate cancer [ 7 ], breast cancer [ 8 ], cervical cancer [ 9 ], pancreatic cancer [ 10 ], melanoma [ 11 ], squamous carcinoma of the head and neck [ 12 ], papillary carcinoma of the thyroid [ 13 ], and glioma [ 14 ]. Therefore, mPGES-1 has become an important target for the treatment of acute and chronic inflammatory diseases and cancers as shown in Supplementary Figure S1 [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

mPGES-1 Inhibitor Discovery Based on Computer-Aided Screening: Pharmacophore Models, Molecular Docking, ADMET, and MD Simulations

et al. 2023

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mPGES-1 is an enzyme, which, when activated by inflammatory factors, can cause prostaglandin E synthesis. Traditional non-steroidal anti-inflammatory drugs are capable of inhibiting prostaglandin production, yet they can also cause gastrointestinal reactions and coagulation disorders. mPGES-1, the enzyme at the conclusion of prostaglandin production, does not cause any adverse reactions when inhibited. Numerous studies have demonstrated that mPGES-1 is more abundant in cancerous cells than in healthy cells, indicating that decreasing the expression of mPGES-1 could be a potential therapeutic strategy for cancer. Consequently, the invention of mPGES-1 inhibitors presents a fresh avenue for the treatment of inflammation and cancer. Incorporating a database of TCM compounds, we collected a batch of compounds that had an inhibitory effect on mPGES-1 and possessed IC50 value. Firstly, a pharmacophore model was constructed, and the TCM database was screened, and the compounds with score cut-off values of more than 1 were retained. Then, the compounds retained after being screened via the pharmacodynamic model were screened for docking at the mPGES-1 binding site, followed by high-throughput virtual screening [HTVS] and standard precision [SP] and super-precision [XP] docking, and the compounds in the top 20% of the XP docking score were selected to calculate the total free binding energy of MM-GBSA. The best ten compounds were chosen by comparing their score against the reference ligand 4U9 and the MM-GBSA_dG_Bind score. ADMET analysis resulted in the selection of ten compounds, three of which had desirable medicinal properties. Finally, the binding energy of the target protein mPGES-1 and the candidate ligand compound was analyzed using a 100 ns molecular dynamics simulation of the reference ligand 4U9 and three selected compounds. After a gradual screening study and analysis, we identified a structure that is superior to the reference ligand 4U9 in all aspects, namely compound 15643. Taken together, the results of this study reveal a structure that can be used to inhibit mPGES-1 compound 15643, thereby providing a new option for anti-inflammatory and anti-tumor drugs.

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PGE2 signaling and its biosynthesis-related enzymes in cholangiocarcinoma progression

et al. 2014

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Prostaglandin E2 (PGE2) involves in progression of various chronic inflammation-related cancers including cholangiocarcinoma (CCA). This study aimed to determine the role of PGE2 signaling, its biosynthesis-related enzymes in a clinical prognosis, and their targeted inhibition in CCA progression. The immunohistochemical staining of cyclooxygenase (COX)-1, COX-2, mPGES-1, EP1, and EP4 was examined in CCA tissues, and their expressions were compared with clinicopathological parameters. The effect of PGE2 on levels of its signaling molecules was examined in CCA cell lines using proteome profiler array. The suppression of mPGES-1 using a small-molecule inhibitor (CAY10526) and small interfering RNA (siRNA) was determined for growth and migration ability in CCA cells. The results indicated that strong expressions of COX-1, COX-2, mPGES-1, EP1, and EP4 were found in CCA tissues as 87.5, 47.5, 52.5, 55, and 80 % of frequencies, respectively. High mPGES-1 expression was significantly correlated with tumor stages III-IV (p = 0.001), lymph node metastasis (p = 0.004), shorter survival (p = 0.009), and prognostic indicator of CCA patients (HR = 2.512, p = 0.041). Expressions of COX-1, COX-2, and EP receptors did not correlate with data tested from patients. PGE2 markedly enhanced protein levels of integrinα6, VE-cadherin, Jagged1, and Notch3, and CAY10526 suppressed those protein levels as well as PGE2 production in CCA cells. CAY10526 and siRNA mPGES-1 markedly suppressed mPGES-1 protein levels, growth, and migration abilities of CCA cell lines. In conclusion, PGE2 signaling strongly promotes CCA progression. Therefore, inhibition of PGE2 synthesis by suppression of its biosynthesis-related enzymes could be useful for prevention and treatment of CCA.

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Expression and Significance of Microsomal Prostaglandin Synthase-1 (mPGES-1) and Beclin-1 in the Development of Prostate Cancer

Cited by 9 publications

References 35 publications

Chemoresistance is associated with Beclin-1 and PTEN expression in epithelial ovarian cancers

Chemoresistance is associated with Beclin-1 and PTEN expression in epithelial ovarian cancers

mPGES-1 Inhibitor Discovery Based on Computer-Aided Screening: Pharmacophore Models, Molecular Docking, ADMET, and MD Simulations

PGE2 signaling and its biosynthesis-related enzymes in cholangiocarcinoma progression

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