title: Everolimus and zoledronic acid--a potential synergistic treatment for lung adenocarcinoma bone metastasis.
abstract: Non-small-cell lung cancer (NSCLC) frequently metastasizes to bone. It is known that zoledronic acid is cytostatic to tumors, and everolimus, the inhibitor for mammalian target of the rapamycin, could inhibit many types of cancer. Herein, we evaluated the effect of zoledronic acid alone and in combination with everolimus on treating lung adenocarcinoma bone metastasis in vitro and in vivo. Mice treated with zoledronic acid in combination with everolimus had more apoptotic lung cancer cells and more cells were arrested in the G1/G0 phase. The phosphorylation of p70S6K was inhibited in the combination treatment group. Lung cancer cell invasion was also significantly inhibited in the group with combination treatment in vitro. Bone nuclear scans revealed more metastatic lesions in controls compared with those in the combination treatment group. Bone scans and radiographic images indicated that combination therapy significantly reduced bone metastasis. The moderate survival rate suggested that the drug combination was synergistic, which can delay NSCLC bone metastasis and prolong survival in vivo.
authors.affiliation: Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou 310022, China.
authors.forename: Zhengbo
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Nuclear Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Shunfang
authors.initials: S
authors.lastname: Yang
authors.affiliation: Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Thoracic Surgery, Shanghai Cancer Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China lushun1964@126.com.
authors.forename: Shun
authors.initials: S
authors.lastname: Lu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary*; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D000068338:Everolimus; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D000068338:Everolimus; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D020123:Sirolimus
keywords: bone metastasis; everolimus; lung adenocarcinoma; zoledronic acid