1. Academic Validation
  2. Proteasome inhibitors attenuates mitoxantrone-triggered immunogenic cell death in prostate cancer cells

Proteasome inhibitors attenuates mitoxantrone-triggered immunogenic cell death in prostate cancer cells

  • Med Oncol. 2020 Nov 19;37(12):116. doi: 10.1007/s12032-020-01445-y.
Wei Wei 1 Haibin Li 2 Guoan Zhang 3 Ying Zhang 2 Ke Wu 2 Rongrong Bao 2 Gege Wang 2 Han Zheng 2 Yong Xia 2 Changlin Li 4
Affiliations

Affiliations

  • 1 Center for Experimental Medicine, School of Public Health, Jining Medical University, Jining, 272067, China.
  • 2 Institute of Precision Medicine, Jining Medical University, Jining, 272067, China.
  • 3 Institute of Cancer Pathology Research, Jining Medical University, Jining, 272067, China.
  • 4 Institute of Precision Medicine, Jining Medical University, Jining, 272067, China. [email protected].
Abstract

Both mitoxantrone (MTX) and Proteasome inhibitors efficiently trigger immunogenic cell death (ICD) in Cancer cells. However, whether the combination of MTX and Proteasome inhibitors can synergistically enhance ICD remains unknown. In this study, we showed that the Proteasome inhibitors bortezomib (BZM) and carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132) impaired MTX-induced ICD in prostate Cancer cells, as measured using ICD biomarkers and dendritic cell activation in vitro. Mice vaccinated with RM-1 mouse prostate Cancer cell line treated with BZM or MG132 in combination with MTX showed enhanced tumor growth, and shortened tumor-free, and worse overall survival compared with those treated with MTX alone. In conclusion, we demonstrated that Proteasome inhibitors (BZM or MG132) attenuated MTX-induced ICD, suggesting that Proteasome activation was required for MTX-induced ICD.

Keywords

Bortezomib; Immunogenic cell death; Mitoxantrone; Proteasome inhibitor.

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