The Anti-proliferative Activity of GnRH Through Downregulation of the Akt/ERK Pathways in Pancreatic Cancer

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.

SKA1 promotes tumor metastasis via SAFB-mediated transcription repression of DUSP6 in clear cell renal cell carcinoma

“…Ingenuity Pathway Analysis (IPA) was utilized for relevant diseases and pathway analysis based upon differential expression genes. As shown in Supplementary Table 3B, GNRH signaling, known to be a crucial regulator in various types of malignancies [22][23][24], is the most significantly enriched pathway. The top five diseases and processes were angiogenesis, cell migration, cell movement, cell movement of tumor cell lines, and development of vasculature (Supplementary Table 3C).…”

Atractylenolide‐1 affects glycolysis/gluconeogenesis by downregulating the expression of TPI1 and GPI to inhibit the proliferation and invasion of human triple‐negative breast cancer cells

“…Finally, the activation of AKT can overcome cell cycle arrest at both G1 and G2 phases (Suo, Chang, Xu, & Ji, 2019).…”

“…AKT also activates NF‐κB by modulating IκB kinase (IKK), leading to the transcription of pro‐survival genes. Finally, the activation of AKT can overcome cell cycle arrest at both G1 and G2 phases (Suo, Chang, Xu, & Ji, 2019).…”

New drug delivery strategies targeting the GnRH receptor in breast and other cancers

“…GnRH-I pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 GnRH-II pGlu-His-Trp-Ser-His-Gly-Trp-Tyr-Pro-Gly-NH2 GnRH-III pGlu-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH2 pancreatic cancer. Inhibition of GnRH also led to higher invasiveness in Panc1 cells (Suo et al 2019). GnRH analogs were found to inhibit metastasis of MCF-7 and MDA-MB-231 breast cancer cell lines (von Alten et al 2006) in addition to prostate cancer cell lines DU145 and PC3 (Dondi et al 2006).…”