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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
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
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
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
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
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]