• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.519-526
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• 2021

In a search for effective PPAR-γ agonists, 110 clinical drugs were screened via molecular docking, and 9 drugs, including parecoxib, were selected for subsequent biological evaluation. Molecular docking of parecoxib to the ligand-binding domain of PPAR-γ showed high binding affinity and relevant binding conformation compared with the PPAR-γ ligand/antidiabetic drug rosiglitazone. Per the docking result, parecoxib showed the best PPAR-γ transactivation in Ac2F rat liver cells. Further docking simulation and a luciferase assay suggested parecoxib would be a selective (and partial) PPAR-γ agonist. PPAR-γ activation by parecoxib induced adipocyte differentiation in 3T3-L1 murine preadipocytes. Parecoxib promoted adipogenesis in a dose-dependent manner and enhanced the expression of adipogenesis transcription factors PPAR-γ, C/EBPα, and C/EBPβ. These data indicated that parecoxib might be utilized as a partial PPAR-γ agonist for drug repositioning study.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.627-633
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• 2015

Background: To study the effect of parecoxib, a novel cyclooxygenase-2 selective inhibitor, on the radiation response of colorectal cancer (CRC) cells and its underlying mechanisms. Materials and Methods: Both in vitro colony formation and apoptosis assays as well as in vivo mouse xenograft experiments were used to explore the radiosensitizing effects of parecoxib in human HCT116 and HT29 CRC cells. Results: Parecoxib sensitized CRC cells to radiation in vitro with a sensitivity enhancement ratio of 1.32 for HCT116 cells and 1.15 for HT29 cells at a surviving fraction of 0.37. This effect was partially attributable to enhanced apoptosis induction by parecoxib combined with radiation, as illustrated using an in vitro apoptosis assays. Parecoxib augmented the tumor response of HCT116 xenografts to radiation, achieving growth delay more than 20 days and an enhancement factor of 1.53. In accordance with the in vitro results, parecoxib combined with radiation resulted in less proliferation and more apoptosis in tumors than radiation alone. Radiation monotherapy decreased microvessel density (MVD) and microvessel intensity (MVI), but increased the hypoxia level in xenografts. Parecoxib did not affect MVD, but it increased MVI and attenuated hypoxia. Conclusions: Parecoxib can effectively enhance radiation sensitivity in CRC cells through direct effects on tumor cells and indirect effects on tumor vasculature.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3977-3980
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• 2015

Background: To investigate the effects of preemptive analgesia with parecoxib sodium on haemodynamics and plasma stress hormones in surgical patients with thyroid carcinoma. Materials and Methods: Fifty-seven patients with thyroid carcinoma who underwent thyroidectomy selectively in Laiwu Hospital Affiliated to Taishan Medical University and Binzhou People's Hospital were selected and randomly divided into three groups, 19 cases in each group. The control group was intravenously injected 0.9% sodium chloride injection before anesthesia induction; trial group I was intravenously injected with parecoxib sodium 20 min before anesthesia induction; based on trial group I, trial group II was injected with parecoxib sodium again 12 h after surgery. The levels of plasma norepinephrine (NE), cortisol (Cor) and blood glucose before, 12 and 24 h after surgery and changes of haemodynamics before surgery, at the end of surgery and 12, 24 and 48 h after surgery were compared in the three groups. Besides, visual analogue scale (VAS) scores were recorded 4, 8, 12 and 24 h after surgery. Results: 12 and 24 h after surgery, the levels of plasma NE and Cor in three groups rose dramatically (P<0.05 or (P<0.01); The levels of plasma NE and Cor in trial groups I and II were evidently lower than in control group (P<0.05 or P<0.01), and those in trial group II slightly lower than in trial group I. 12 h after surgery, the heart rates (HR) and systolic pressures (SBP) in trial groups I and II increased obviously by comparison to surgery before (P<0.05 or P<0.01), but gradually returned to the preoperative level. HR, SBP and diastolic pressures (DBP) in trial groups I and II at the end of surgery and 12 h after surgery were all lower than in the control group, and significant differences were present (P<0.05 or (P<0.01). At 4, 8, 12 and 24 h after surgery, VAS scores in trial groups I and II were markedly lower than in the control group (P<0.05 or (P<0.01), the scores in trial group II being the lowest. Conclusions: Combined application of parecoxib sodium for preemptive analgesia before anesthesia and after surgery can effectively reduce the levels of plasma stress hormones and improve analgesic effects in surgical patients with thyroid carcinoma, and without conspicuous impact on haemodynamics.