Chemotherapy Resistance: The role of proteasomal degradation and heat shock response

Proteasomal degradation is crucial to prevent the accumulation of cellular damage. The removal of the damage is a required process for healthy organisms to keep the integrity while in cancer cells this situation may induce drug resistance. Regarding chemotherapy for the cancer treatment, degradation mechanisms such as proteasomal system and autophagy have been focused recently and proteasomal inhibition in cancer cells have been shown to induce autophagy. This induced pathway may prevent the cancer cells from death or can cause autophagic cell death which is an important reason for chemotherapy resistance. There are many preclinic studies to improve the results and on the other hand heat shock proteins are accepted to be protective which may bring new approach. In our laboratory, several cancer cell lines have been tested from different aspects of proteasomal activity. HCT116 colon cancer cell line was used to test the role of HSP70 and proteasome inhibition on autophagic cell death. In this direction, heat shock treatment has been applied to the cells which is also an applied process for cancer patients. Cell viability, proteasome activity, degradation of long-lived proteins, and the expressions of HSP70, LC3, beclin1, caspase 9 and PARP have been analysed. Additionally, mouse hippocampal cell line is used to test the proteasomal activity in relation to heat shock proteins which highlighted another important point for the chemothrapy resistance with antioxidant gene expressions. Different breast cancer cell lines have also confirmed the role of proteasomal degradation in the failure of chemotherapy. Supported by TUBITAK COST-CM1001-110S281 and TUBITAK 212T156