Abstract
Gonadotropin-releasing hormone (GnRH) has been demonstrated to exert anti-proliferative functions on various tumor cells in endometrial, ovarian, bladder, or prostate cancer as a part of the autocrine system. In addition, the expression levels of GnRH and its receptor had been identified in breast cancer or non-reproductive cancers, such as glioblastoma and pancreatic cancer. Previous studies have reported abnormal GnRH expression in several malignant tumors, suggesting that GnRH and its receptor might be essential for tumourigenesis. In the present study, we attempted to clarify the mechanisms underlying GnRH function in cell proliferation in pancreatic cancer. Our results indicated that GnRH expression might be essential for the malignancy of pancreatic cancer. We then found that GnRH overexpression can induce cell apoptosis through activating the Bcl-2/Bax pathway and autophagy might be involved in the GnRH-mediated apoptosis in Panc1 cells. Further investigation showed that the inhibition of GnRH may promote tumor invasion and migration through upregulation of MMP2 expression in pancreatic cancer cells. Moreover, our results indicated that GnRH can regulate the Akt/ERK1/2 pathways to promote cell proliferation by inhibiting cell apoptosis in Panc1 cells. Therefore, our finding exhibited that the regulation of GnRH expression may be essential for tumourigenesis in pancreatic cancer, and might be a potential target for the treatment of the patients with pancreatic cancer.
Highlights
Pancreatic cancer is a rare, but lethal malignant tumor, which is the third most deadly cancer, and there were over 50,000 estimated cases and 43,090 deaths in the United States [1]
Since previous studies indicated that Gonadotropin-releasing hormone (GnRH) and its receptor were expressed in various malignant tumors [10, 11, 13], we expected that GnRH expression might be associated with malignancy in pancreatic cancer
After analyzing the overall staining intensity, we found that GnRH immunostaining was very weak in normal and early-stage pancreatic cancer specimens (I and II), whereas the highexpression of GnRH was observed in the advanced pancreatic cancer specimens (II, III, and IV), suggesting that GnRH expression might be related to the malignancy in pancreatic cancer (Figure 1B)
Summary
Pancreatic cancer is a rare, but lethal malignant tumor, which is the third most deadly cancer, and there were over 50,000 estimated cases and 43,090 deaths in the United States [1]. A recent study indicated that GnRH agonists have strong anti-tumor activity, which can reduce cell proliferation in ovarian, endometrial, and breast cancer cells [13]. A GnRH antagonist can cause the reduction of cell proliferation in a dose- and time-dependent manner in various tumors [13,14,15,16]. All this evidence indicates that GnRH may play an important role as a modulator of tumor growth in various malignant tumors, which might provide potential targets for therapy with GnRH analogs
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