Synergistic growth inhibition by sorafenib and cisplatin in human osteosarcoma cells
Authors: Jianwu Zhao
Rongpeng Dong
Mingyang Kang
Shanyong Zhang
Qu Yang
Journal: Oncology Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: Molecular-targeted therapy; osteosarcoma; Sorafenib; Cisplatin; combinatorial treatment
Affiliations: Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin 130042, P.R. China.

Abstract:  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. 

Retracted: Yes

PubPeer comments:
 Figs 3E, 4A.  western blot analysis of MMP-2 and MMP-9 protein expression following treatment with SOR and CDDP alone or combination ;  Cells were treated with SOR and CDPP alone or both for 4 h. Western blot analysis were performed using specific antibodies against the indicated proteins . ![file] 3E shares its loading control with Fig 3B of [Sang et al (2016)](http: www.ijcem.com files ijcem0019312.pdf).  PIK3R3 on ... protein level were determined in 786-O cells transfected with si-PIK3R3 or si-NC by... western blot. ![file] Also Fig 4 of [Li et al (2015)] . ![] , 
 Fig 5A.  Images of tumor tissue from different treatments collected after sacrifice at day 22. ![file] I have not tried to mark up the CDDP+SOR or the SOR bands, for fear of obscuring the change in texture around the 2nd tumor in the former, or the 5th tumor in the latter. For comparison, *[left]* Fig 6A from .[Qu et al (2015)] .  Images of tumor tissue with different plasmid treatments collected after sacrifice at day 21. *[right]* Fig 6A from [Liu et al (2015)] .  Graphs of the tumor tissue from the different groups . ![file] *[left]* Fig 7A from [Zhang et al (2015)] .  Images of tumor tissue with different groups collected after sacrifice at day 28 . *[right]* Fig 7A from [Tian et al (2015)] .  Images of tumor tissues in the different mouse groups collected after sacrifice at day 28. ![file] UPDATE: Fig 7A from [Li et al (2016)] .  Photographs of tumor tissue from nude mice 35 days after inoculation . ![file] I have concerns. , 
 *[right]* Fig 2A from [**Yang et al (2015)**] .  Cell DNA content distribution in each phase after treatment with SOR and CDDP alone or in combination . *[Upper left]* Fig 3A from [Tian et al (2015)] .  Effects of miR-218 on the cell cycle progression of Eca109 cells as measured by flow cytometric analysis. *[lower left]* Fig 2e from [Qu et al (2016)] . Cell  cycle distribution... determined in MG63 cells after transfected with miR-150 or miR-NC . ![file] , 
 Retracted [16 July 2021] . --------------------------- Following the publication of this paper, it was drawn to the Editors attention by a concerned reader that certain of the western blotting data shown in Figs. 3A and 4A, and tumor images in Fig. 5A, bore unexpected similarities to data appearing in different form in other articles by different authors. Owing to the fact that some of the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to *Oncology Reports*, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused ,