The effect of inhibiting ER stress on response to Paclitaxel in ovarian and colorectal cancer cells

Abstract

The endoplasmic reticulum (ER) is the organelle responsible for carrying out the vital function of protein synthesis and secretion. Cellular disturbances cause the accumulation of unfolded proteins and induce a condition known as ER stress. This activates an evolutionary conserved multi-signalling pathway called the unfolded protein response (UPR) which tries to restore the cell homeostasis. However, prolonged ER stress causes the UPR to activate its apoptotic pathways to cause cell death. Studies have shown that ER stress and UPR induction influence the development of cancer through either its adaptive or apoptotic arms. In addition, it has been evidenced that UPR activation can sensitise cancer cells to certain chemotherapy drugs to cause either chemo-efficiency or chemo-resistance. The chemotherapy drug, paclitaxel, has been shown to use ER stress induced apoptosis to cause cell death. However, it is not exactly clear what mechanism paclitaxel uses to induce ER stress-mediated apoptosis. This research investigated paclitaxel response in ovarian and colorectal cancer cell lines by inhibiting known pathways of ER stress. From the results obtained, it was found that paclitaxel causes cellular death, but whether it does via the specific induction of an ER stress pathway is still not evident and needs further investigation.