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Table 4 Relevant studies of NCTD anti-angiogenesis, anti-VM, and anti-lymphangiogenesis

From: Insight into norcantharidin, a small-molecule synthetic compound with potential multi-target anticancer activities

Anticancer activities

Cancers

Cell lines

Basic mechanisms

Pathways

Accompanying roles

Experiment

References

Anti-angiogenesis

Gallbladder cancer

GBC-SD

Inhibiting capillary-like tube formation of HUVECs in vitro; destroying angiogenesis and CAM capillaries; decreasing xenograft MVD and vascular perfusion in vivo; downregulating VEGF, Ang-2; upregulating TSP, TIMP-2

 

Prolonging xenograft-mice survival

In vitro

[84]

GBC-SD

Lower MVD and PCNA/apoptosis ratio, smaller tumor volume; down-regulating VEGF and Ang-2, and up-regulating TSP and TIMP2; MVD positively correlating with VEGF, Ang-2n and negatively correlating with TSP and TIMP2

  

In vitro

In vivo

[83]

Colorectal cancer

HCT116

Inhibiting xenograft growth and tumor angiogenesis in vivo; reducing migration, adhesion and vascular network tube formation of HUVECs in vitro; downregulating VEGF and VEGFR-2

Downregulating VEGF and VEGFR-2

 

In vivo

[85]

CT26

Inhibiting viability, adhesion, migration, capillary-like tube formation of HUVECs, and the release of pro-angiogenic factors from HUVECs; inducing anoikis; down-regulating VEGF, integrin β1, vimentin, p-JNK and p-ERK

Down-regulating VEGF and inhibiting MAPK (JNK/ERK) signaling

Without renal or hepatic toxicity

In vitro

In vivo

[14]

LOVO

Inhibiting VEGF-induced proliferation, migration, invasion, capillary tube formation of HUVECs and LOVO proliferation; inhibiting tumor angiogenesis and tumor growth in vivo; inhibiting VEGFR2/MEK/ERK pathway

Blocking VEGFR2/MEK/ERK

  

[86]

Anti-VM

Gallbladder cancer

GBC-SD

Inhibiting proliferation, invasion, migration, VM formation in vitro and in vivo; downregulating EphA2, FAK and Paxillin

Blocking the EphA2/FAK/Paxillin signaling pathway

Prolonging xenograft mice survival

In vitro

In vivo

[13]

GBC-SD

Inhibiting proliferation, growth, invasion, migration and VM formation in vitro and in vivo; downregulating MMP-2, MT1-MMP, PI3-K, Ln-5γ2

Suppression of the PI3-K/MMPs/Ln-5γ2 signaling pathway

  

[91]

GBC-SD

MMP‑2, MT1‑MMP relating tumor VM In vitro; a poor survival in VM+ patients with high MMP‑2, MT1‑MMP expression; inhibiting tumor growth, VM formation, VM hemodynamic in vivo; inhibiting proliferation, invasion, migration and VM‑like networks in vitro; downregulating MMP‑2 and MT1‑MMP in vivo and in vitro; thus, enhancing TIMP‑2 antitumor and anti‑VM activities

Enhancing TIMP-2 anti-VM via downregulating MMP-2 and MT1-MMP

With TIMP-2 synergistic effect; prolonging xenograft mice survival

 

[92]

Melanoma

A375

 

Suppressing MMP-2 expression

 

In vitro

In vivo

[83]

Anti-lymphangiogenesis

HLEC

HDLECs

Inhibiting proliferation, migration, invasion, lymphatic tube formation (lymphangiogenesis), inducing apoptosis; downregulating VEGF-C, VEGF-D and VEGFR-3 expression

Blocking VEGF-C,-D, VEGFR-3

 

In vitro

[98]

HDLECs

Inhibiting growth, lymphatic tube formation; inducing apoptosis; downregulating VEGF-C and VEGF-D expression

Downregulating the expression of VEGF-C and VEGF-D

  

[99]

Colorectal cancer

HT-29

S-phase cell-cycle arrest; Inhibiting proliferation, migration, invasion, lymphatic tube formation in vitro and tumor growth and lymphangiogenesis in vivo; downregulating Ki-67, Bcl-2, LYVE-1, D2-40, CK20 and their LMVD, and VEGF-A, VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in vitro and in vivo

Blocking the VEGF-A,-C,-D, VEGFR-2, -3 “multi-points priming” mechanisms

With mF4-31C1 or Sorafenib synergistic effect

In vitro

In vivo

[100]

AML

TSC-null cell 21-101

Inhibiting proliferation of TSC2−, TSC2+ cells with rapamycin

 

An additive effect between rapamycin and NCTD in inhibiting lymphangiogenesis

In vitro

[171]