Sensitisation of colorectal cancer cells to anti-tumor immune responses

Colorectal cancer is the third most common cancer in the world and the five-year survival rate of those diagnosed in advanced stages is very low. Current standard treatments are insufficient in the treatment of advanced cancers. On the other side, activation of tumor-specific immune responses holds great promise in the treatment of such cancers. Bortezomib is an FDA-approved chemotherapy agent that is used in the treatment of various cancers and studies have shown that bortezomib can trigger immunogenic cell death. Epirubicin, another chemotherapeutic drug, is known as an anthracycline agent which can be used with other chemotherapeutic drugs, particularly in the treatment of breast cancer. The aim of this study was to increase the expression of important genes involved in immunogenic cell death by using low doses of two chemotherapeutic agents, bortezomib and epirubicin, in combination. For this purpose, normal colorectal cell line and metastatic two colorectal cancer cell lines were treated with bortezomib and epirubicin in variety of doses and the minimum toxicity effects on these cells were determined by MTT assays. The effects of these two agents on the expression of DR4, DR5 and NKG2DL genes which are involving in immunogenic cell death were then analyzed by RT-PCR. The obtained data showed that the combination treatment significantly increased the transcription expression of DR4, DR5 and NKG2DL genes in colorectal tumor cells, but did not show a significant increase in normal colorectal cells. Thus, the use of bortezomib and epirubicin at low doses may increase the immunogenicity of tumor cells which can contribute to the activation of tumor-specific immune responses.