PURPOSE: Orally absorbable anticancer medications have great advantages for conventional cancer therapies to patients. Here we evaluated the potent anticancer effect of orally absorbable LHD, a chemical conjugate of low-molecular-weight heparin and deoxycholic acid, on tumor graft growth models. METHODS: We characterized the angiogenic factors, such as VEGF, heparanase, and MMPs, of murine squamous cell carcinoma (SCC7), melanoma (B16F10) or lung carcinoma (LLC1). Two weeks after oral administration of LHD into these cancer-cell-bearing mice, we evaluated the antiangiogenic activity of LHD. RESULTS: Although all cancer cells expressed the angiogenic factors, SCC7 cells had much higher angiogenic potential and grew rapidly after implantation into mice. When orally administered, LHD delayed tumor graft growth regardless of cancer types. Particularly, LHD powerfully diminished the SCC7-derived tumor growth. Also, the expression of angiogenic factors in all kinds of tumor tissues was decreased, thereby attenuating the neovascularization in tumor tissue. CONCLUSION: Our study shows that LHD has potent anticancer and antiangiogenic effect on at least three kinds of tumor cells. LHD can be specifically used for preventing neovascularization in tumor tissue because it has therapeutical potential as an antiangiogenic drug and can be orally absorbed.
PURPOSE: Orally absorbable anticancer medications have great advantages for conventional cancer therapies to patients. Here we evaluated the potent anticancer effect of orally absorbable LHD, a chemical conjugate of low-molecular-weight heparin and deoxycholic acid, on tumor graft growth models. METHODS: We characterized the angiogenic factors, such as VEGF, heparanase, and MMPs, of murinesquamous cell carcinoma (SCC7), melanoma (B16F10) or lung carcinoma (LLC1). Two weeks after oral administration of LHD into these cancer-cell-bearing mice, we evaluated the antiangiogenic activity of LHD. RESULTS: Although all cancer cells expressed the angiogenic factors, SCC7 cells had much higher angiogenic potential and grew rapidly after implantation into mice. When orally administered, LHD delayed tumor graft growth regardless of cancer types. Particularly, LHD powerfully diminished the SCC7-derived tumor growth. Also, the expression of angiogenic factors in all kinds of tumor tissues was decreased, thereby attenuating the neovascularization in tumor tissue. CONCLUSION: Our study shows that LHD has potent anticancer and antiangiogenic effect on at least three kinds of tumor cells. LHD can be specifically used for preventing neovascularization in tumor tissue because it has therapeutical potential as an antiangiogenic drug and can be orally absorbed.
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