Table 1.

A summary of previously published studies related to the present study.

Study	Title	Conclusions
Pabst et al. (2015) [11]	The influence of geranyl geraniol on human oral keratinocytes after bisphosphonate treatment: An in vitro study	Bisphosphonate treatment had negative effects on human oral keratinocytes (HOKs)
Ziebart et al. (2011) [8]	Bisphosphonates: restriction for vasculogenesis and angiogenesis: inhibition of cell function of endothelial progenitor cells and mature endothelial cells in vitro	The nitrogen-containing bisphosphonates, pamidronate, and zoledronate, had the greatest impact on human umbilical vein endothelial cells (HUVECs)
Kim et al. (2016) [18]	Zoledronic acid is an effective radiosensitizer in the treatment of osteosarcoma	Zoledronic acid decreased the phosphorylation of PI3K-Akt and MAPK pathway proteins
Tang et al. (2010) [19]	Bisphosphonates suppress insulin-like growth factor 1-induced angiogenesis via the HIF-1α/VEGF signaling pathways in human breast cancer cells	Inhibitory effects of bisphosphonates on the HIF-1α/VEGF axis are associated with PI3K/Akt/mTOR signaling pathways
Treda et al. (2016) [13]	EGFR activation resulted in cell death, ndependent of PI3K/Akt/mTOR in the AD293 cell human embryonic kidney cell line	PI3K, Akt, and mTOR were shown to be downstream proteins of the epidermal growth factor receptor (EGFR)
Bhattacharya et al. (2015) [21]	T11TS inhibits angiopoietin-1/Tie-2 signaling, EGFR activation, and the Raf/MEK/ERK pathway in brain endothelial cells, inhibiting angiogenesis in a glioma model	EGFR was expressed by endothelial cells, not only in epithelial cells

MAPK – mitogen-activated protein kinase; HIF-1 – hypoxia inducible factor-1; VEGF – vascular endothelial growth factor; T11TS – T11-target structure.