Cyclooxygenase‐2 inhibitor suppresses tumour progression of prostate cancer bone metastases in nude mice

Abstract

Objective• To assess whether celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor with anti-cancer properties, has an inhibitory effect on tumour establishment and progression of prostate cancer (PCa) bone metastases. Materials and Methods• PC-3 stable luciferase-expressing cells were injected into male nude mice by intracardiac (i.c.) and intratibial (i.t.) injections, and the effect of celecoxib on bone metastases was then recorded using bioluminescence image analysis.• In cases of chemoprevention, mice received 3 mg/kg celecoxib from 1 week before cell implantation until the end of the study, and to test the therapeutic effect, mice received celecoxib 1 week after cell implantation until the end of the study.• Tumour tissue samples were histologically examined and COX-2 expression was quantified at the protein level. Results• Celecoxib significantly decreased cell viability and the proliferation of human PCa cells in vitro in a dose-dependent manner.• Bone metastases were detected after i.c. injection in nude mice.• Celecoxib (15 ppm) administered before i.c. injection did not inhibit the cellular metastatic potential, as the numbers of bone metastases were similar in both groups. However, celecoxib did decrease metastatic progression in the osseous environment when cells were injected directly into the tibia (P < 0.05).• At the protein level, COX-2 expression was significantly decreased in the celecoxib treatment group (P < 0.01). Conclusion• In a preclinical mice model, celecoxib administered orally at the standard human dose inhibits the progression of established PCa bone metastases.

The metabolic co-regulator PGC1α suppresses prostate cancer metastasis

“…As an additional approach, we sought to analyse metastatic tumour re-initiation capacity by means of local injection of PCa cells at the metastatic site. Since PCa exhibits osteotropic nature 42 , we carried out intra-tibial injection of cells and the appearance of tumour masses in the bone was monitored 43 ( Fig. 3j ).…”

Docetaxel plus oral metronomic cyclophosphamide: A phase II study with pharmacodynamic and pharmacogenetic analyses in castration‐resistant prostate cancer patients

“…CXB has shown antiangiogenic properties and antitumor and antimetastatic activities in mouse models of prostate adenocarcinoma when administered at the standard human dose, as a result of both COX‐2‐independent and COX‐2‐dependent mechanisms . Furthermore, CXB clinical trials in patients with PSA recurrence have shown interesting activity in terms of slowing PSA kinetics without relevant toxicities, and our group has successfully investigated a metronomic regimen of oral cyclophosphamide and CXB in advanced pretreated CRPC patients .…”

IL-1β-Mediated Repression of microRNA-101 Is Crucial for Inflammation-Promoted Lung Tumorigenesis

“…Cyclooxygenase-2 (COX2), a member of the COXs that are responsible for the production of inflammatory mediator prostaglandins, has been identified as a key inflammation-associated molecule in response to cigarette smoking, cytokines, and growth factors, and COX2 is known to promote the initiation and progression of NSCLC as well as other types of human epithelial tumors (3)(4)(5)(6)(7). Interestingly, inhibition of COX2 by nonsteroid anti-inflammatory drugs (NSAID) has been shown to be an effective approach in prevention and therapy of NSCLC and several other types of cancers by both epidemiologic and experimental data (8)(9)(10)(11)(12)(13). Such findings have confirmed the role of inflammation in the pathogenesis of NSCLC, but the molecular connections between inflammation and NSCLC have remained largely elusive.…”