Abstract
More than 25% of patients diagnosed with endometrial carcinoma have invasive primary cancer accompanied by metastases. Growth hormone-releasing hormone (GHRH) plays an important role in reproduction. Here, we examined the effect of a GHRH antagonist on the motility of endometrial cancer cells and the mechanisms of action of the antagonist in endometrial cancer. Western blotting and immunohistochemistry (IHC) were used to determine the expression of the GHRH receptor protein. The activity of Twist and N-cadherin was determined by Western blotting. Cell motility was assessed by an invasion and migration assay. GHRH receptor siRNA was applied to knockdown the GHRH receptor in endometrial cancer cells. The GHRH antagonist inhibited cell motility in a dose-dependent manner. The GHRH antagonist inhibited cell motility and suppressed the expression of Twist and N-cadherin, and the suppression was abolished by GHRH receptor siRNA pretreatment. Moreover, the inhibition of Twist and N-cadherin with Twist siRNA and N-cadherin siRNA, respectively, suppressed cell motility. Our study indicates that the GHRH antagonist inhibited the cell motility of endometrial cancer cells through the GHRH receptor via the suppression of Twist and N-cadherin. Our findings represent a new concept in the mechanism of GHRH antagonist-suppressed cell motility in endometrial cancer cells and suggest the possibility of exploring GHRH antagonists as potential therapeutics for the treatment of human endometrial cancer.
Highlights
Endometrial cancer is the most common, and second most lethal, gynecological malignancy
We examined the effect of Growth hormone-releasing hormone (GHRH) antagonist on the cell migration and invasion of two human endometrial cancer cell lines, Ishikawa and ECC-1, as well as the underlying molecular mechanisms of action involved
GHRH antagonist inhibits human endometrial cancer cell migration and invasion To examine whether GHRH receptor (GHRH-R) is involved in regulation of human endometrial cancer cell migration and invasion, Ishikawa and ECC-1 were treated with a GHRH antagonist, MIA-602
Summary
Endometrial cancer is the most common, and second most lethal, gynecological malignancy. Twist has been characterized as a critical transcription factor that regulates the expression of N-cadherin in cancer cells [13, 14]. In different types of cancer, treatment with GHRH antagonist decreases cell migration and invasion [15, 16]. Based on these studies, we hypothesized that GHRH antagonist inhibits human endometrial cancer cell migration and invasion by downregulating the expression of N-cadherin. We examined the effect of GHRH antagonist on the cell migration and invasion of two human endometrial cancer cell lines, Ishikawa and ECC-1, as well as the underlying molecular mechanisms of action involved. Our data suggest that GHRH antagonist might be a potential molecule for the clinical treatment of human endometrial cancer
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