Galangin Alleviates Tumor Progression and Metastasis in Intraperitoneal Ovarian Cancer Model via Inhibiting Janus Kinase 1/Signal Transduction and Activator of Transcription 3 Signaling

Abstract

To investigate the impact of galangin on tumor progression and metastasis in intraperitoneal ovarian cancer model. Ovarian cancer cells were treated with DMSO or galectin, cell viability was detected by MTS or acid phosphatase assay, SKOV3 cells were transfected with STAT3 targeted shRNA and the expression of signal transduction-related proteins in cells was analyzed by immunoblotting assay, the expression of IL-6, IL-2, INF-y was estimated by enzyme-linked immunosorbent assay the peritoneal metastasis model of ovarian cancer was established using shSTAT3 transfected or untransfected SKOV3 cells and treated with galangin or DMSO. Tumor mass, number of small tumor nodules and ascites volume were detected in the mouse model. Ovarian cancer-bearing mice treated with galangin showed a dramatic decreased tumor burden as demonstrated by the 25 times-reduced total weight of small tumor nodules, 60%-reduced primary tumors, attenuated luciferase activity and completely blocked ascites production. Moreover, galangin inhibited cell viability in vitro in a concentration-dependent manner. Further, p-STAT3 was suppressed by galangin treatment both in vivo and vitro. Galangin inhibited the expression of p-JAK1, the upstream signaling of p-STAT3 and IL-6 in the downstream. Meanwhile, knockdown of STAT3 by shSTAT3 transfection mimicked the therapeutic effects of galangin in vivo and vitro. Galangin supresses IL-6 secretion, peritoneal metastasis and ascites production by inhibiting JAK1/STAT3 signaling.