title: MG132 enhances the radiosensitivity of lung cancer cells in vitro and in vivo.
abstract: Radiotherapy is a common treatment modality for lung cancer, however, radioresistance remains a fundamental barrier to attaining the maximal efficacy. Cancer cells take advantage of the ubiquitin-proteasome system (UPS) for increased proliferation and decreased apoptotic cell death. MG132 (carbobenzoxyl-leucinyl-leucinyl-leucinal‑H), a specific and selective reversible inhibitor of the 26S proteasome, has shown anticancer effect in multiple types of cancers. Previously, we have reported that MG132 enhances the anti‑growth and anti-metastatic effects of irradiation in lung cancer cells. However, whether MG132 can enhance the radiosensitivity in lung cancer cells in vitro and in vivo is still unknown. In this study, we found that MG132 increased apoptosis and dicentric chromosome ratio of A549 and H1299 cells treated by irradiation. Radiation-induced NF-κB expression and IκBα phosphorylation was attenuated in MG132 plus irradiation-treated cells. The in vivo model of H1299 xenografts of nude mice showed that the tumor size of MG132 plus irradiation treated xenografts was smaller than that of irradiation, MG132 or the control group. Moreover, MG132 plus irradiation group showed significant reduced Ki67 expression. Taken together, these results demonstrate that MG132 enhances the radiosensitivity through multiple mechanisms in vitro and in vivo.
authors.affiliation: School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Jihua
authors.initials: J
authors.lastname: Nie
authors.affiliation: School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Wenjiong
authors.initials: W
authors.lastname: Sheng
authors.affiliation: School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Han
authors.initials: H
authors.lastname: Cao
authors.affiliation: School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Wenhao
authors.initials: W
authors.lastname: Shen
authors.affiliation: School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Aijing
authors.initials: A
authors.lastname: Dong
authors.affiliation: The Core Laboratory of Suzhou Cancer Center and Department of Radiotherapy of Suzhou Municipal Hospital, Suzhou, Jiangsu 215001, P.R. China.
authors.forename: Jundong
authors.initials: J
authors.lastname: Zhou
authors.affiliation: School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Cao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D066298:In Vitro Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D007976:Leupeptins / Q000008:administration & dosage* / Q000494:pharmacology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D051379:Mice; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000494:pharmacology; D047368:Tumor Burden / Q000187:drug effects / Q000528:radiation effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D019394:Ki-67 Antigen; D007976:Leupeptins; D011838:Radiation-Sensitizing Agents; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde