Thus, we investigate whether adiponectin and its receptors influence ovarian cancer development. adiponectin and various ovarian steroid hormone and growth factor pathways in ovarian cancer cells. Introduction Ovarian cancer remains the leading cause of death among women, with an estimated 150,000 annual deaths worldwide [1]. Due to its non-specific symptoms, most cases of ovarian cancer are detected when the disease has advanced to a late stage that associates with poor survival. Thus, approaches that would increase its early detection are urgently needed to reduce mortality. Ovarian cancer can be classified into three types based on the cell of its origin, namely, epithelial, stromal, and germ, with each type conferring different histopathological features and clinical outcomes [2]. Epithelial ovarian cancer is the most common ovarian malignancy; it originates in epithelial cells found on the surface of the ovary and accounts for ~?80C90% of ovarian malignancies. Stromal tumors, on the other hand, account for ~?7% of ovarian malignancies, and the most frequently diagnosed stromal tumor type is the granulosa cell tumor (GCT). There is emerging ABT-639 hydrochloride evidence to indicate that obesity is the main independent risk factor for ovarian cancer [3C5]. Although the correlation between ovarian cancer and obesity has been linked to hormones, it is not clear how they can trigger malignancy in obese women. Hormones and growth factors have important functions in regulating cell proliferation, differentiation, and apoptosis. For example, 17-estradiol (E2), progesterone (P4), and insulin-like growth factor 1 (IGF-1) have all been proposed to influence ovarian cancer development [6, 7]. Adipokines, hormones secreted from adipose tissues that may promote obesity, may also affect malignancy development. Adiponectin, an adipokine with a molecular weight of 30?kDa, is found in the serum, where it exists in four isoforms, namely, trimeric (90?kDa), ABT-639 hydrochloride hexameric (180?kDa), and high-molecular-weight (360 and 400?kDa) isoforms [8]. At a serum concentration of 5C30?g/ml, it is the most abundant circulating peptide hormone. In obese adults, however, the serum adiponectin level is usually reduced [9]. Adiponectin has been reported to act as an anti-tumor factor by ABT-639 hydrochloride inhibiting cancer cell proliferation [10, 11]. Other studies report a role for adiponectin in obesity-associated cancer such as those of the breast, cervix, and endometrium. However, the role of adiponectin in ovarian cancer has been studied much less. For example, Jin et DFNA56 al. reported that adiponectin levels were significantly lower in ovarian cancer patients than in healthy individuals, but the reason for this is not clear [12]. Furthermore, the biological actions of adiponectin are mediated through interactions with its receptor subtypes, AdipoR1 and AdipoR2. Li et al. showed that a low AdipoR1 expression level in cancerous ovarian tissues serves as an independent prognostic indicator of the disease [13]. In the human granulosa ABT-639 hydrochloride KGN cell line, AdipoR1 functions in cell survival, whereas AdipoR2 regulates steroid production [14]. Several endogenous, as well as exogenous factors, including insulin, thiazolidinediones, metformin, and bisphenol A (BPA), can regulate the production and secretion of adiponectin in the 3T3-L1 adipocyte cell line [15C18]. On the other hand, several lines of evidence indicate that endocrine disrupting chemicals, such as BPA, can induce obesity [19, 20]. BPA, a commercial product commonly used in polycarbonate plastics and epoxy resins [21], possesses estrogenic activity and promotes ovarian cancer cell proliferation [22, 23] and migration [24]. Epidemiological studies report that humans have detectable serum levels of not only BPA, but also its halogenated derivatives, tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) [25C27]. We aimed to investigate whether adiponectin and its receptors, AdipoR1 and AdipoR2, are expressed in human epithelial ovarian cancer cell lines. We also examined whether BPA and its analogs ABT-639 hydrochloride can affect the expression of adiponectin and its receptors in ovarian cancer cells. The effects of adiponectin on cell proliferation and apoptosis were also examined. Finally, we investigated whether E2, P4, and IGF-1 can regulate.
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