Increased Temperature Facilitates Adeno-Associated Virus Vector Transduction of Colorectal Cancer Cell Lines in a Manner Dependent on Heat Shock Protein Signature

Abstract

Colorectal cancer (CRC) is one of the most common cancers in human population. A great achievement in the treatment of CRC was the introduction of targeted biological drugs and solutions of chemotherapy, combined with hyperthermia. Cytoreductive surgery and HIPEC (hyperthermic intraperitoneal chemotherapy) extends the patients’ survival with CRC. Recently, gene therapy approaches are also postulated. The studies indicate the possibility of enhancing the gene transfer to cells by recombinant adeno-associated vectors (rAAV) at hyperthermia. The rAAV vectors arouse a lot of attention in the field of cancer treatment due to many advantages. In this study, the effect of elevated temperature on the transduction efficiency of rAAV vectors on CRC cells with different origin and gene profile was examined. The effect of heat shock on the penetration of rAAV vectors into CRC cells in relation with the expression of HSP and AAV receptor genes was tested. It was found that the examined cells under hyperthermia (43°C, 1 h) are transduced at a higher level than in normal conditions (37°C). The results also indicate that studied RKO, HT-29, and LS411N cell lines express HSP genes at different levels under both 37°C and 43°C. Moreover, the results showed that the expression of AAV receptors increases in response to elevated temperature. The study suggests that increased rAAV transfer to CRC can be achieved under elevated temperature conditions. The obtained results provide information relevant to the design of new solutions in CRC therapy based on the combination of hyperthermia, chemotherapy, and gene therapy.

Amplifying Curcumin’s Antitumor Potential: A Heat-Driven Approach for Colorectal Cancer Treatment

“…78 While the pairing of curcumin and HIPEC is an intriguing prospect, more work will need to study mechanisms of cell death, long-term toxicity, and therapeutic effects in clinical trials. Many novel agents, such as immunotherapies, [79][80][81] oncolytic viruses, 82 and nanotechnology, have shown promise in vitro but must be further tested in an in vivo setting to determine their impact on patient outcomes. Only once rigorous clinical trials have been conducted, and we will have a more complete understanding of the efficacy and safety of combining novel therapeutics such as curcumin with HIPEC in colorectal cancer.…”

Mosaic Recombinant Adeno-associated Virus Vector rAAV/DJ/CAG for Targeted Gene Delivery to Melanoma Cells Metastasized to the Lung

“…Among the viral carriers, great interest has been shown for adeno-associated viruses, rAAV, due to their high safety profile. They can be used for gene therapy of metastatic lung tumors such as melanoma, which has been shown in post-mortem analysis that in as much as 70% of cases metastasizes to the lungs (38,77). In our studies, rAAV/GFP vectors were used to identify the melanoma cells that metastasize to the lungs.…”