|
| Drugs | Experiment/cancer model | Effect | References |
|
| siRNA VEGF-C | Mouse mammary tumor model (C166-siVEGFC) | Reduction in tumor lymphangiogenesis, lymph node metastasis, and spontaneous lung metastasis | [193] |
|
| Human monoclonal antibody VC (anti-VEGF-C) | In vitro binding affinity of antibody was tested | (i) Bind with high specificity and affinity to full processed mature form of human VEGF-C
(ii) Inhibit the binding of VEGF-C to VEGFR-2 and VEGFR-3 | [194] |
|
| VEGFR31-Ig | Mouse model of a highly metastatic human hepatocellular carcinoma (HCCLM3) | (i) Simultaneously bind VEGF-A, VEGF-C.
(ii) Block both tumor angiogenesis and lymphangiogenesis, effectively inhibit primary tumor growth, metastasis to lung and lymph node | [195] |
|
| VD1 monoclonal Ab (anti-VEGF-D) | Immunodeficient mice, 293EBNA express VEGF-D (mAbs raised to VDH of hVEGF-D (antagonists)) | Reduce the LN metastasis from 61% to 0% | [98] |
|
| Monoclonal Ab to VEGFR-3 | Regeneration of adult lymphatic vessels | Block the regeneration of lymphatic vessels in adult | [196] |
|
| VEGFR-3 monoclonal antibody | Mouse model of MDA-MB-435/GFP human breast cancer transfected with human VEGF-C cDNA | Suppress tumor lymphangiogenesis and restrict metastatic spread to lymph nodes and distant organs | [197] |
|
| Soluble VEGFR-3 (VEGFR-3-Ig) | Highly metastasis human lung cancer cells (LNM35) stably expressing VEGFR-3-Ig or recombinant adenovirus expressing VEGFR-3-Ig were injected to LNM35 tumor-bearing mice | (i) Inhibition of intra- and peritumoral lymphangiogenesis
(ii) Metastasis to LN was inhibited
(iii) Metastasis to lung occurred in all mice group | [198] |
|
| Soluble VEGFR-3 (VEGFR-3-Rg) | Immunocompetent rat model induced with highly metastatic MT-450 cancer cells expressing VEGFR-3 soluble | (i) Reduction in the number of peritumor lymphatic vessels
(ii) Suppression of metastasis formation both in regional LNs and lungs | [199] |
|
| Soluble VEGFR-3 decoy receptor (sVEGFR3-Fc) | Mouse model of human melanoma, human prostate injected with recombinant adeno-associated viral vector sVEGFR3-Fc (rAAV-sVEGFR3-Fc) Treatment before tumor implantation | (i) Melanoma: inhibit LN metastasis, but have less effect on lung metastasis
(ii) Prostate: inhibit LN and lung metastasis
(iii) Inhibition of tumor-associated lymphangiogenesis | [192] |
|
| Soluble VEGFR-3 | Mouse model of prostate cancer (PC-3): subcutaneously or surgical orthotopic implantation | Reduction in intratumoral lymphatics, but metastasis to LN was not significantly affected | [200] |
|
| Ki23057 | Mouse model of gastric cancer induced by orthotopic inoculation of OCUM-2MLN cells | (i) Ki23057 is a tyrosine kinase inhibitor, block autophosphorylation of VEGFR-3
(ii) Reduced significantly lymphatic invasion and lymphangiogenesis
(iii) Reduced size of orthotopic tumors and number of metastatic LN | [201] |
|
| Anti- neutropilin-2 | Mouse model of breast adenocarcinoma (66C14) and rodent glioblastoma (C6) | Reduction in tumor lymphangiogenesis, metastasis to sentinel lymph nodes and distant organs | [189] |
|
| Celecoxib (COX-2 inhibitor) | Mouse model of highly metastasis human lung adeocarcinoma | Suppression of the lymphangiogenesis and lymph node metastasis through downregulation of VEGF-C expression. | [202] |
|
| Antagonists of integrin α4β1 | Mouse model of Lewis lung carcinoma and B16 melanoma cancer | Significant suppression of lymphangiogenesis and metastasis | [203] |
|
