Bortezomib potentiates antitumor activity of mitoxantrone through dampening Wnt/β-catenin signal pathway in prostate cancer cells

  • BMC Cancer. 2021 Oct 13;21(1):1101. doi: 10.1186/s12885-021-08841-1.
Ying Zhang  1 ,  Qiuzi Liu  1 ,  Wei Wei  2 ,  Guoan Zhang  3 ,  Siyuan Yan  1 ,  Rongrong Dai  1 ,  Ying Sun  1 ,  Dubo Su  1 ,  Shun Lv  4 ,  Yong Xia  1 ,  Jing Li  5 ,  Changlin Li  6
Affiliations
  • 1. Institute of Precision Medicine, Jining Medical University, Jining, 272067, China.
  • 2. Center for Experimental Medicine, School of Public Health, Jining Medical University, Jining, 272067, China.
  • 3. Institute of Cancer Pathology Research, Jining Medical University, Jining, 272067, China.
  • 4. Laboratory animal center, Jining Medical University, Jining, 272067, China.
  • 5. Department of Histology and Embryology, School of Medicine, Nankai University, Tianjin, 300071, China.
  • 6. Institute of Precision Medicine, Jining Medical University, Jining, 272067, China. [email protected].
PMID: 34645397 DOI: 10.1186/s12885-021-08841-1
Abstract

Background: 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.

Methods: Anticancer 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.

Results: BZM 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.

Conclusions: This study demonstrates that BZM enhances MTX-induced anti-tumor effects by inhibiting the Wnt/β-catenin signaling pathway in prostate Cancer cells.

Keywords
Bortezomib; Cell proliferation; Mitoxantrone; Wnt/β-catenin signaling.
Products