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. 2017 Jun;13(6):4378-4384.
doi: 10.3892/ol.2017.5953. Epub 2017 Mar 29.

Identification of candidate drugs for the treatment of metastatic osteosarcoma through a subpathway analysis method

Xin Li  1 , Ming-Lan Yan  1 , Qian Yu  1
Affiliations

Identification of candidate drugs for the treatment of metastatic osteosarcoma through a subpathway analysis method

Xin Li et al. Oncol Lett. 2017 Jun.

Abstract

Osteosarcoma (OS) is the third most frequent type of cancer in adolescents and represents >56% of all bone tumors. In addition, metastatic OS frequently demonstrates resistance to conventional chemotherapy; thus, the development of novel therapeutic agents for the treatment of patients with metastatic OS is warranted. In the present study, the metabolic mechanisms underlying OS metastasis were investigated using a subpathway analysis method and lead to the identification of candidate drugs for the treatment of metastatic OS. Using the GSE14827 microarray dataset from the Gene Expression Omnibus database, 546 differentially expressed genes were identified between samples from patients with OS who did or did not develop metastatic OS. Furthermore, nine significantly enriched metabolic subpathways were identified, which may be involved in OS metastasis. Finally, using an integrated analysis of metastatic OS-associated subpathways and drug-affected subpathways, 98 small molecule drug candidates capable of targeting the metastatic OS-associated subpathways were identified. This method identified existing anti-cancer drugs, including semustine, in addition to predicting potential drugs, such as lansoprazole, for the treatment of metastatic OS. Transwell and wound healing assays demonstrated that lansoprazole reduced the invasiveness and migration of U2OS cells. These small molecule drug candidates identified through a bioinformatics approach may provide insights into novel therapy options for the treatment of patients with metastatic OS.

Keywords: drugs; metabolic subpathways; metastatic osteosarcoma; network.

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Figures

Figure 1.
Figure 1.
Small molecule drugs and their corresponding subpathways. Triangular nodes represent subpathways and circular nodes represent drugs. Subpathways of the same color are included in the same entire pathway.
Figure 2.
Figure 2.
U2OS cell invasion following lansoprazole treatment was assessed using the Transwell assay. (A) Representative images of invasive cells (magnification, ×200). (B) Relative levels of invasive cells compared with the control. *P<0.05 vs. the control group.
Figure 3.
Figure 3.
Effect of lansoprazole (100 µM) on the migration of cultured U2OS cells, assessed through a wound healing assay.
See this image and copyright information in PMC

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References

    1. He H, Ni J, Huang J. Molecular mechanisms of chemoresistance in osteosarcoma (Review) Oncol Lett. 2014;7:1352–1362. - PMC - PubMed
    1. Chou AJ, Gorlick R. Chemotherapy resistance in osteosarcoma: Current challenges and future directions. Expert Rev Anticancer Ther. 2006;6:1075–1085. doi: 10.1586/14737140.6.7.1075. - DOI - PubMed
    1. Longhi A, Errani C, de Paolis M, Mercuri M, Bacci G. Primary bone osteosarcoma in the pediatric age: State of the art. Cancer Treat Rev. 2006;32:423–436. doi: 10.1016/j.ctrv.2006.05.005. - DOI - PubMed
    1. He JP, Hao Y, Wang XL, Yang XJ, Shao JF, Guo FJ, Feng JX. Review of the molecular pathogenesis of osteosarcoma. Asian Pac J Cancer Prev. 2014;15:5967–5976. doi: 10.7314/APJCP.2014.15.15.5967. - DOI - PubMed
    1. Broadhead ML, Clark JC, Myers DE, Dass CR, Choong PF. The molecular pathogenesis of osteosarcoma: A review. Sarcoma. 2011;2011:959248. doi: 10.1155/2011/959248. - DOI - PMC - PubMed