The STAT3 Inhibitor Galiellalactone Effectively Reduces Tumor Growth and Metastatic Spread in an Orthotopic Xenograft Mouse Model of Prostate Cancer.

Abstract

UNLABELLED:

Signal transducer and activator of transcription 3 (STAT3) is known to be involved in the progression of prostate cancer (PCa) and is a key factor in drug resistance and tumor immunoescape. As a result, it represents a promising target for PCa therapy. We studied the effects of the STAT3 inhibitor galiellalactone (GL) on tumor growth and metastatic spread in vitro and in vivo. The effect of GL on cell viability, apoptosis, and invasion was studied in vitro using androgen-independent DU145 and DU145-Luc cell lines. For in vivo studies, mice were injected orthotopically with DU145-Luc cells and treated with daily intraperitoneal injections of GL for 6 wk. GL significantly reduced the growth of the primary tumor and the metastatic spread of PCa cells to regional and distal lymph nodes in vivo. Treatment with GL also resulted in decreased cell proliferation and increased apoptosis compared with controls. In vitro, GL reduces the viability and invasive abilities of DU145-Luc cells and induces apoptosis. Our results showed that tumor growth and early metastatic dissemination of PCa can be significantly reduced by GL, indicating its potential use as a therapeutic compound in advanced metastatic PCa.

PATIENT SUMMARY:

In this study, we tested the STAT3 inhibitor galiellalactone (GL) in an animal model of PCa. We found that mice treated with GL had smaller primary tumors and decreased lymph node metastases compared with mice treated with vehicle. GL has potential for treating advanced metastatic PCa.

• Authors: Giacomo Canesin, Susan Evans-Axelsson, Rebecka Hellsten, Olov Sterner, Agnieszka Krzyzanowska, Tommy Andersson, Anders Bjartell
• Journal: European urology (Eur Urol) Vol. 69 Issue 3 Pg. 400-4 (Mar 2016) ISSN: 1873-7560 [Electronic] Switzerland
• PMID: 26144873 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Lactones
• STAT3 Transcription Factor
• STAT3 protein, human
• galiellalactone

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Humans
• Lactones (pharmacology)
• Lymphatic Metastasis
• Male
• Mice, Nude
• Neoplasm Invasiveness
• Prostatic Neoplasms (drug therapy, metabolism, pathology)
• STAT3 Transcription Factor (antagonists & inhibitors, metabolism)
• Signal Transduction (drug effects)
• Time Factors
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays