<p>Rapamycin suppresses angiogenesis and lymphangiogenesis in melanoma by downregulating VEGF-A/VEGFR-2 and VEGF-C/VEGFR-3 expression</p>

Lymphangiogenesis
DOI: 10.2147/ott.s205160 Publication Date: 2019-06-12T19:37:37Z
ABSTRACT
Background: Cutaneous melanoma is a highly malignant tumor which tends to metastasize in the early stage and leads poor prognosis. Hematogenous lymphatic metastasis are common dissemination of melanoma. Rapamycin, an mTOR inhibitor, was reported have anti-angiogenic anti-lymphangiogenic properties. Aim: The aim this study investigate if rapamycin can inhibit formation blood vessels Methods: A xenograft model generated by subcutaneously transplanting A375 human cells into back immunodeficient mice. Two weeks after cell transplantation, injected intraperitoneally every other day seven times. Then, tumors were harvested.Hematoxylin-eosin (H-E)staining, immunohistochemical staining, Western blot, quantitative PCR performed observe pathological structure tumor, distribution vessels, expression signal pathway, VEGF-A/VEGFR-2, VEGF-C/VEGFR-3. Results: results showed that CD34(+) LYVE-1(+) decreased peritumor intratumor region rapamycin-treated tumors. Expression p-4EBP1 p-S6K1 proteins downregulated. both mRNAs VEGF-A/VEGFR-2 VEGF-C/VEGFR-3 Conclusion: In conclusion, suppresses angiogenesis lymphangiogenesis blocking pathway subsequently downregulating Therefore, targeted therapy via may control hematogenous melanoma, even prolong patients' survival time. Keywords: rapamycin, angiogenesis,
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