The present study represents the first time that celecoxib, a special COX-2 inhibitor widely used in clinics, was explored to normalize the tumor microenvironment and to improve tumor nanotherapeutics delivery using a human-derived A549 tumor xenograft as the solid tumor model.
The aim of the study was to analyze the expression of monocyte chemoattractant protein-1, interleukin-6 (IL-6), tumor necrosis factor-α, inducible isoform of nitric oxide synthase (iNOS), cyclooxygenase-2, and osteopontin in vitro in two different tumor cell lines under hypoxia (pO<sub>2</sub>≈1.5 mmHg) and/or acidosis (pH=6.6) for up to 24 hours since hypoxia and acidosis are common characteristics of solid tumors.
Cyclooxygenase 2 (COX-2) and phosphorylated Akt1 (p-Akt1) are associated with tumor spreading, cell proliferation, high metabolism, and angiogenesis in solid tumors.
The enzyme cyclooxygenase 2 is an inducible enzyme expressed at sites of inflammation and in a variety of malignant solid tumors such as endometrial cancer (EC).
Role of cyclooxygenase 2 (COX-2) is well documented in the pathogenesis of solid tumors, but little is known about its occurrence and function in hematologic neoplasms.
COX-2 upregulation was associated with downregulation of KAI-1/CD82, a metastasis suppressor molecule that has been associated with the metastatic potential of several solid tumors.
Overexpression of the inducible enzyme, cyclooxygenase-2 (COX-2), has been discovered in a variety of adult solid tumors and numerous studies have shown COX-2 inhibitors to have significant antiproliferative effects.