Abstract
Patients with ovarian serous carcinoma are generally diagnosed at an advanced disease stage. The standard treatment for these patients is maximal debulking surgery followed by platinum-taxane combination chemotherapy. Despite initially responding well, more than half of patients become refractory to first-line chemotherapy. Upregulation of protein arginine methyltransferase 1 (PRMT1) expression has been demonstrated to methylate apoptosis signal-regulated kinase 1 and inhibit its activity, thereby contributing to chemoresistance. The present study investigated the association between PRMT1 expression and sensitivity to platinum-based chemotherapy in 51 patients with ovarian serous carcinoma (International Federation of Gynecology and Obstetrics stages III and IV), and the effect of RNA interference-mediated downregulation of PRMT1 on the sensitivity of ovarian cancer cells to cisplatin and carboplatin in vitro. Immunohistochemistry of tumor specimens was used to compare the expression levels of PRMT1, a Cell Counting Kit-8 assay and small interfering RNA transfection were performed for chemosensitivity assays, and reverse transcription-quantitative PCR was used to examine PRMT1 mRNA expression. Patients were divided into platinum-sensitive (n=26) and platinum-resistant (n=25) groups. PRMT1 expression was significantly lower in the platinum-sensitive group than in the platinum-resistant group (P=0.019). When patients were categorized according to PRMT1 expression, those in the low PRMT1 expression group were more sensitive to platinum-based chemotherapy than those in the high PRMT1 expression group (P=0.01). Additionally, in vitro experiments revealed that suppression of PRMT1 expression by siRNA significantly increased the sensitivity of human ovarian serous carcinoma cells to cisplatin and carboplatin (P<0.05). In conclusion, PRMT1 expression could predict sensitivity to platinum-based chemotherapy in patients with ovarian serous carcinoma.
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