Abstract
BackgroundBortezomib (BZM), alone or in combination with other chemotherapies, has displayed strong anticancer effects in several cancers. The efficacy of the combination of BZM and mitoxantrone (MTX) in treating prostate cancer remains unknown.MethodsAnticancer effects of combination of BZM and MTX were determined by apoptosis and proliferation assay in vivo and in vitro. Expression of β-Catenin and its target genes were characterized by western blot and Real-time PCR.ResultsBZM significantly enhanced MTX-induced antiproliferation in vivo and in vitro. Mice administered a combination of BZM and MTX displayed attenuated tumor growth and prolonged survival. BZM significantly attenuated MTX-induced apoptosis. Moreover, the combination of BZM and MTX contributed to inhibition of the Wnt/β-Catenin signaling pathway compared to monotherapy.ConclusionsThis study demonstrates that BZM enhances MTX-induced anti-tumor effects by inhibiting the Wnt/β-Catenin signaling pathway in prostate cancer cells.
Highlights
Bortezomib (BZM), alone or in combination with other chemotherapies, has displayed strong anticancer effects in several cancers
The combination treatment was significantly better at inhibiting tumor growth compared with individual drug treatment (Fig. 1A, B)
The combination treatment significantly prolonged survival to longer duration compared to individual drug treatment (Fig. 1C)
Summary
Bortezomib (BZM), alone or in combination with other chemotherapies, has displayed strong anticancer effects in several cancers. The efficacy of the combination of BZM and mitoxantrone (MTX) in treating prostate cancer remains unknown. Aberrant activation of Wnt/β-Catenin signaling is involved in several cancers, including colorectal cancers [3], hepatocellular carcinomas [4], melanoma [5], pancreas cancer [6], adrenocortical carcinoma [7], and prostate cancer [8]. The Wnt pathway is considered a potential therapeutic target for the development of effective tumor treatment strategies. MTX, a type-2 DNA topoisomerase inhibitor [9], has been widely used as chemotherapy for the treatment of metastatic prostate cancer [10, 11]. BZM shows potent antitumor activity for solid tumors in preclinical studies [18], encouraging data have not been confirmed in the clinic therapies [19]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
