The Activity of Medroxyprogesterone Acetate, an Androgenic Ligand, in Ovarian Cancer Cell Invasion

Abstract

Although classified as a progestin, medroxyprogesterone acetate has significant androgenic activity unique from the pure androgen dihydrotestosterone. Our studies suggest that pharmacologic doses of medroxyprogesterone acetate may actually increase the invasive potential of epithelial ovarian cancer cells.

The Role of Androgen Receptor Signaling in Ovarian Cancer

“…It was additionally shown that DHT induced cell motility and invasion of an ovarian cancer line [79]. Methyltrienolone [76] and another AR ligand, medroxyprogesterone [80], also increased the ability of cell invasion of AR-positive ovarian cancer lines, although the latter is classified as a progestin. All of these studies have thus demonstrated in vitro and in vivo data indicating that androgens promote cell proliferation/invasion of ovarian cancer via the AR pathway.…”

“…All of these studies have thus demonstrated in vitro and in vivo data indicating that androgens promote cell proliferation/invasion of ovarian cancer via the AR pathway. Nonetheless, conflicting findings have been documented in two studies that show significant inhibition of the cell viability of 25 primary cultures established from various subtypes of ovarian carcinomas as well as borderline and benign tumors by 0.1 pM–100 nM testosterone [81] and marginal inhibition of ovarian cancer cell invasion by 1 µM DHT [80].…”

Mitogen-Activated Protein Kinase Signal Transduction in Solid Tumors

“…The ovarian cancer cells express AR and respond to androgen with increased proliferation and attenuated apoptosis. Over-expression of AR has been found in ovarian cancer, and once activated, it can stimulate ovarian cancer cell invasion (Gogoi et al, 2008;Ligr et al, 2011), indicating targeting AR is also a promising treatment strategy.…”

Nuclear receptors in ovarian cancer: changing paradigms in cancer therapeutics

“…DHT acts as an agonist for AR, thereby inducing the proliferation and invasiveness of various OVC cells ( 78 , 81 ). However, an intriguing study by Gogoi and colleagues showed that DHT and medroxyprogesterone acetate, an androgenic ligand, act by upregulating the inflammatory cytokines, IL-6 and IL-8 and downregulating the matrix metalloproteinases, MMP-2 and MMP-9 in OVC cells ( 79 ). Similarly, in another study, DHT increased cell proliferation in SKOV3 cells by elevating the IL-6 and IL-8 levels, which was reversed by treatment with an AR antagonist, flutamide ( 78 ).…”