Synergistic growth inhibition by sorafenib and cisplatin in human osteosarcoma cells.
Molecular-targeted therapy has shown promise as a treatment for advanced osteosarcoma (OS). Sorafenib (SOR), a multikinase inhibitor, is the approved systemic drug of choice for OS, but has demonstrated limited benefits due to its toxicity and other adverse effects. Therapy strategies for reducing toxicity include using lower doses of SOR in combination with other complementary agents. Cisplatin (CDDP) has been shown to be a promising anticancer drug against various types of cancer including OS. In the present study, SOR was combined with CDDP to determine whether this combinatorial treatment suppressed tumor growth thereby simultaneously reducing doses of the two drugs for the treatment of OS. Human Saos-2 OS cells were treated with SOR and CDDP, alone and in combination, and the effect of these treatments on cell proliferation, colony formation, cell cycle, apoptosis, migration, and invasion, and involvement in receptor signaling, as well as tumor growth ability in nude mice was determined. It was found that the combination of low concentrations of SOR and CDDP significantly suppressed the cell proliferation, colony formation, migration and invasion, and induced cell apoptosis and cell cycle arrest in the G0/G1 stage, and suppressed tumor growth in a nude mouse model compared to the actions of either agent alone. The results also showed that SOR in combination with CDDP significantly suppressed the phosphorylation of extracellular signal-regulated kinase (ERK), which may contribute to the inhibition of tumor growth. These results suggested that SOR in combination with CDDP acts synergistically in the treatment of OS.
Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin 130042, P.R. China.
Qu
Q
Yang
Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin 130042, P.R. China.
Shanyong
S
Zhang
Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin 130042, P.R. China.
Mingyang
M
Kang
Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin 130042, P.R. China.
Rongpeng
R
Dong
Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin 130042, P.R. China.
Jianwu
J
Zhao
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000008:administration & dosage; D004357:Drug Synergism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D010671:Phenylurea Compounds / Q000008:administration & dosage; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D000077157:Sorafenib; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D010671:Phenylurea Compounds; D017382:Reactive Oxygen Species; D009536:Niacinamide; D000077157:Sorafenib; D048049:Extracellular Signal-Regulated MAP Kinases; D002945:Cisplatin