主催: 公益社団法人日本薬理学会
会議名: 第95回日本薬理学会年会
回次: 95
開催地: Fukuoka
開催日: 2022/03/07 - 2022/03/09
We have established and analyzed "clinically relevant radioresistant (CRR) cells" that can survive exposing to 2 Gy/day X-rays for more than 30 days to overcome cancer treatment resistance. CRR cells show resistance against not only radiation but also docetaxel and hydrogen peroxide (H2O2) which is one of the reactive oxygen species (ROS). It has been shown that CRR cells produce less Fe2+, ROS, and lipid peroxidation compared to the parental cells. Furthermore, we have been reported that the expression of miR-7-5p is upregulated in CRR cells and miR7-5p inhibition loses its radioresistance. Therefore, we inhibited miR-7-5p expression in CRR cells by siRNA and investigated the change of Fe2+, ROS, and lipid peroxidation. As a result, miR-7-5p inhibition decreases the amount of Fe2+, ROS, and Liperfluo, which is one of the ferroptosis markers and detects lipid peroxidation. Moreover, miR-7-5p inhibition decreases the gene expression of Ferritin, the iron-binding protein, and arachidonate 12-lipoxygenase (ALOX12), the lipid oxidation enzyme. It has been reported that the overexpression of ALOX12 enhances the ROS amount and lipid peroxidation by H2O2 treatment. Taken together, our results suggest the possibility to overcome the treatment resistance by inhibiting miR-7-5p.