Although the involvement of type 1 (IP3R1) and type 2 (IP3R2) inositol 1,4,5-trisphosphate receptors in apoptosis induction has been well documented in different cancer cells and tissues, the function of type 3 IP3R (IP3R3) is still elusive. Therefore, in this work we focused on the role of IP3R3 in tumor cells in vitro and in vivo. We determined increased expression of this receptor in clear cell renal cell carcinoma compared to matched unaffected part of the kidney from the same patient. Thus, we hypothesized about different functions of IP3R3 compared to IP3R1 and IP3R2 in tumor cells. Silencing of IP3R1 prevented apoptosis induction in colorectal cancer DLD1 cells, ovarian cancer A2780 cells, and clear cell renal cell carcinoma RCC4 cells, compared to apoptosis in cells treated with scrambled siRNA. As expected, silencing of IP3R3 and subsequent apoptosis induction resulted in increased levels of apoptosis in all these cells. Further, we prepared a DLD1/IP3R3_del cell line using CRISPR/Cas9 gene editing method. These cells were injected into nude mice and tumor's volume was compared with tumors induced by DLD1 cells. Lower volume of tumors originated from DLD1/IP3R3_del cells was observed after 12 days, compared to wild type DLD1 cells. Also, the migration of these cells was lesser compared to wild type DLD1 cells. Apoptosis under hypoxic conditions was more pronounced in DLD1/IP3R3_del cells than in DLD1 cells. These results clearly show that IP3R3 has proliferative and anti-apoptotic effect in tumor cells, on contrary to the pro-apoptotic effect of IP3R1.

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This review describes the mechanisms of immune response following DNA vaccination. The efficacy of DNA vaccines in animal models is highlighted, especially in viral diseases against which no widely accepted vaccination is currently available. Emphasis is given to possible therapeutic vaccination in chronic infections due to persisting virus genomes, such as recurrent herpes (HSV-1 and HSV-2), pre-AIDS (HIV-1) and/or chronic hepatitis B (HBV). In these, the problem of introducing foreign viral DNA may not be of crucial importance, since the immunised subject is already a viral DNA (or provirus) carrier. The DNA-based immunisation strategies may overcome several problems of classical viral vaccines. Novel DNA vaccines could induce immunity against multiple viral epitopes including the conservative type common ones, which do not undergo antigenic drifts. Within the immunised host, they mimic the effect of live attenuated viral vaccines when continuously expressing the polypeptide in question. For this reason they directly stimulate the antigen-presenting cells, especially dendritic cells. The antigen encoded by plasmid elicits T helper cell activity (Th1 and Th2 type responses), primes the cytotoxic T cell memory and may induce a satisfactory humoral response. The efficacy of DNA vaccines can be improved by adding plasmids encoding immunomodulatory cytokines and/or their co-receptors.