Regulation of Fas in response to bortezomib and epirubicin in colorectal cancer cells

Abstract

Bortezomib is a reversible proteasome inhibitor affects the ubiquitin-proteasome mechanism to kill cancer cells, and inhibition of the proteasome modulates the expression of multiple target genes at the transcriptional level. Epirubicin is known as an anthracycline agent that interferes with DNA and RNA synthesis, and it can be used with other chemotherapeutic drugs in the treatment of post-surgical breast cancer. Epirubicin may have an anti-tumor effect against broad-spectrum tumor cells. However, it is a non-specific chemotherapeutic agent that can cause high toxicity if not used in appropriate doses. Here, we hypothesize that a combination treatment of bortezomib and epirubicin will induce immunogenic cell death in colorectal cancer cells by increasing expression of death receptors such as Fas, which will make these cancer cells more susceptible to Fas/FasL mediated tumor cell killing. Our data demonstrate that a combination of bortezomib and epirubicin significantly increases the sensitivity of colorectal carcinoma cells, but not healthy non-malignant epithelial cells, to apoptosis. The combination treatment significantly upregulates the transcriptional activation of Fas in colorectal cancer cells but not in normal cells. Our results suggest that combining bortezomib and epirubicin may simultaneously enhance tumor immunogenicity and the induction of antitumor immunity.

Keywords:

• Bortezomib;
• epirubicin;
• Fas/FasL;
• immunogenic cell death;
• colorectal cancer;
• chemotherapy

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Research Fund of the Tokat Gaziosmanpasa University. Project number: 2017/80.

Notes on contributors

Ercan Cacan

Ercan Cacan received his MS degree from the Georgia Institute of Technology, USA; his PhD in Cellular Molecular Biology from the Georgia State University, USA. He is currently an assistant professor of Tumor Biology and Immunogenetics at the Department of Molecular Biology and Genetics, Tokat Gaziosmanpasa University in Turkey. His main research interests focus on molecular mechanisms of chemoresistance and cancer epigenetics and has published many papers in peer-reviewed journals on these fields.

Zeliha C. Ozmen

Zeliha C. Ozmen received her MS and PhD degrees from Ondokuz Mayis University, Turkey. She is currently an assistant professor of Medical Biochemistry in School of Medicine at Tokat Gaziosmanpasa University in Turkey.