title: Heme oxygenase-1 silencing increases the sensitivity of human osteosarcoma MG63 cells to arsenic trioxide.
abstract: Arsenic trioxide (ATO) has been successfully used to treat leukemia and some solid malignant tumors. Our previous study regarding the effects of ATO on mesenchymal-derived human osteosarcoma MG63 cells showed that heme oxygenase-1 (HO-1) was strongly induced upon treatment with ATO. The present study sought to investigate the effect of silencing HO-1 on the sensitivity of osteosarcoma cells to ATO to determine the potential for therapeutic applications. Small hairpin RNA (shRNA)-mediated interference was used to silence HO-1 in MG63 cells. Viability, apoptosis, and intracellular reactive oxygen species (ROS) of the cells were assessed to evaluate the sensitivity of the cells to ATO as well as the potential mechanisms responsible. shRNA-mediated interference prevented the induction of HO-1, increased cell death, and increased intracellular ROS levels in MG63 cells upon treatment with ATO. Silencing HO-1 increased the susceptibility of MG63 cells to the chemotherapeutic drug ATO by enhancing intracellular accumulation of ROS. Our results suggest that the inhibition of HO-1 could improve the outcome of osteosarcoma treated with ATO.
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, 130021, People's Republic of China.
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Zhong
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Wenxue
authors.initials: W
authors.lastname: Li
authors.forename: Junlian
authors.initials: J
authors.lastname: Gu
authors.forename: Xiuying
authors.initials: X
authors.lastname: Li
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Wang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yue
authors.forename: Yan
authors.initials: Y
authors.lastname: Mu
authors.forename: Jinping
authors.initials: J
authors.lastname: Bai
authors.forename: Ronggui
authors.initials: R
authors.lastname: Li
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001483:Base Sequence; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D017931:DNA Primers; D020868:Gene Silencing; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D010087:Oxides / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D001152:Arsenicals; D017931:DNA Primers; D010087:Oxides; D017382:Reactive Oxygen Species; D051547:Heme Oxygenase-1; D000077237:Arsenic Trioxide