TABLE 1.

Pre‐clinical studies of anti‐angiogenic inhibitors in OS

Class	Drug	In vitro or In vivo	Target	Efficacy	Refs.
Monoclonal antibody	Bevacizumab	In vivo	‐	Angiogenesis; growth↓ apoptosis↑	40
	Bevacizumab	In vivo	‐	Angiogenesis; growth↓	41
	Bevacizumab	In vivo	‐	Angiogenesis; growth↓	42
TKIs	Sorafenib	In vitro and In vivo	ERK1/2; MCL‐1; ezrin pathways	Proliferation; angiogenesis; metastasis↓ apoptosis↑	48
	Sorafenib	In vitro	VEGFR2; RET; MEK/ERK signalling pathway	Proliferation↓	49
	Sorafenib	In vitro	‐	Proliferation↓ apoptosis↑	50
	Sorafenib+everolimus	In vitro and In vivo	mTOR pathway	Proliferation; growth; metastasis; angiogenesis↓ apoptosis↑	56
	Apatinib	In vitro and In vivo	VEGFR2/STAT3/BCL‐2 signal pathway	Proliferation; growth↓ apoptosis; autophagy↑	60
	Apatinib+doxorubicin	In vitro	STAT3/Sox2 pathway	Chemoresistance↓ sensitivity to doxorubicin↑	62
	Pazopanib+LDM topotecan	In vitro and In vivo	‐	Angiogenesis; growth↓	68
	Pazopanib	In vitro and In vivo	VEGF	Metastasis↓	22
Endostatin	Endostar+cisplatin	In vivo	VEGF;MMP.‐9	Proliferation; angiogenesis↓	88
	Endostar+combretastatin A4 phosphate	In vivo	‐	Growth; angiogenesis↓	89
	Endostar+adriamycin	In vivo	‐	Growth; angiogenesis↓	90
Traditional Chinese herbal medicine	Modified Siwu decoction	In vivo	VEGF; KDR; Flt‐1	Growth; angiogenesis; metastasis↓	94
	Thymoquinone	In vitro and In vivo	NF‐κB; XIAP; survivin; VEGF	Growth; angiogenesis↓	95
	Cryptotanshinone	In vitro	VEGF	Growth; angiogenesis↓	96
	Triptolide	In vitro	Wnt/β‐Catenin signalling	Angiogenesis↓ Autophagy apoptosis↑	97

↑: Up‐regulation, ↓: down‐regulation.