Investigation of the toll-like receptor 1/2 dependent drug resistance in ovarian cancer

Ovarian cancer is the deadliest type of the gynecological cancers. Although chemotherapy applications include efficient treatment methods, the majority of the patients develop chemoresistance associated with poor survival rates. In addition, there is a lack of therapeutic approaches that can properly prevent or eliminate chemoresistance in ovarian cancer. Toll-like receptors (TLRs) are molecules that play important roles in innate and adaptive immunity with stimulating the release of pro-inflammatory cytokines and interferons in leukocytes for helping to establish an immune response against pathogens and tumors. However, current studies have shown that besides the immune cells, cancer cells can also express TLRs. Furthermore, these cells can significantly improve their proliferative properties and chemoresistance mechanisms with these molecules and associated signaling pathways. Since TLRs can play crucial roles in both the immune system and cancer progression with chemoresistance, it is possible to define them "double-edged swords". In this study, it was aimed to investigate in detail the relationship between TLRs and ovarian cancer chemoresistance, which is currently a new subject for the literature. For this purpose, potential effects of the heterodimeric TLR1/2 on the cancer progression and chemoresistance were evaluated. Proliferation data confirmed that TLR1/2 and associated signaling pathways increase cell division in ovarian cancer cells and desensitize them to the traditional chemotherapy agent cisplatin. In addition, with the Real-Time PCR experiments, it was determined that this receptor can cause changes in the regulation of chemoresistance related genes such as BCL2A1, GSTP1, and ABCB1, depending on the time intervals. Consequently, this study reveals that chemoresistance mechanisms in ovarian cancer can be associated with TLR1/2 mediated signaling pathways.