Cyclooxygenase Inhibitors in Epithelial Ovarian Cancer Treatment

Abstract

Epithelial ovarian cancer (EOC) is the fifth most common cause of cancer mortality among women. At present, EOC is treated with one or in a combination of treatments, commonly debulking surgery, combining a platinum-based and a taxane-based therapy; however, the patients have a risk of injury to the bowel, bladder, ureter, and vessels during surgery and many of them suffer from severe adverse effects caused by chemotherapy. Pharmaceutical inhibition of cyclooxygenase (COX) might be an important therapeutic tool in cancer treatment, as COX contributes to cancer progression by upregulating the levels of downstream metabolites. In this review article, we have discussed the role of COX in cancer progression and the therapeutic use of COX inhibitors in the treatment of EOC with subsequent clinical studies and future management. Usually, gonadotropins can promote prostaglandin E2 production in EOC cells via COX-1 and -2 upregulations through the PI3K/AKT signaling pathway. Several reports have shown that treatment of EOC cells with COX-1- and COX-2-specific inhibitors exhibits a therapeutic effect on EOC both in vitro and in vivo. However, more clinical investigations are needed to develop therapeutic COX inhibitors for the prevention and treatment of EOC without adverse effects.

Cross-talk between SIM2s and NFκB regulates cyclooxygenase 2 expression in breast cancer

“…Additionally, expression of COX-2 is frequently observed in patients with invasive disease and is associated with DCIS recurrence. Furthermore, the therapeutic benefit of inhibiting COX-2 has been observed in the colon, esophagus, lung, bladder, breast, and prostate cancers [18, 19, 25–35]. Thus, it is logical to expect that inhibition of COX-2 signaling in breast cancer patients could enhance overall prognosis.…”

NSAID–Au(I) Complexes Induce ROS-Driven DAMPs and Interpose Inflammation to Stimulate the Immune Response against Ovarian Cancer

“…To visually confirm the structures of these complexes as well as to gain insight into the coordination chemistry and structural parameters of the complexes, B3 (for the sake of simplification, the gold(I)− alkynyl complex with naproxen (Npx) was named Npx-Au) was crystallized after slow evaporation in CH 2 Cl 2 /n-hexane solution at room temperature and its structure was characterized by X-ray diffraction. As shown in Figure 2 and Tables S1−S7, the molecular structure of complex Npx-Au was a linear alkynyl gold(I)−phosphane complex with common C�C and Au−P bond lengths of 1.202 (15) S4). The results showed that its spectrum did not change significantly over 3 days, but the hydrogen spectrum peak disappeared due to proton exchange between the amine (NH) and D 2 O.…”

“…It has been proven that the expression of COX-2 is associated with chemoresistance and poor patient prognosis in ovarian cancer . Encouraging results were reported that COX-1 or COX-2 inhibitors prevented epithelial ovarian cancer cells (EOC) both in vitro and in vivo, which presented a promising strategy in the prevention and treatment of EOC. , The inhibition of COX, reducing “inflammogenesis” of the TME, may be a promising therapy for the treatment of cancers . Accordingly, nonsteroidal anti-inflammatory drugs (NSAIDs) have exhibited potential anticancer effects.…”

Driving Immune Responses in the Ovarian Tumor Microenvironment

“…Depletion of L-arginine in the TME via expression of arginase-1 and inducible nitric oxide synthase (NOS-1) is thought to directly inhibit T cell function and result in cell cycle arrest ( 142 ). Disruption of this process may be achieved in vitro by inhibiting upstream inflammatory cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) or phosphodiesterase-5 (PDE-5) signaling ( 143 ). Similarly, use of PDE-5 inhibitors such as sildenafil and tadalafil, which are already FDA approved for non-cancer indications, is being tested in combination trials in a variety of solid tumors.…”