The Mechanisms Of Nobiletin And Osthole Suppress The Melanoma Proliferation And Migration

With environmental pollution and uv radiation enhancement, the incidence of skin cancer shows the tendency of increase year by year, the skin cancer melanoma is the leading cause of cancer mortality.studies have shown that the metastatic melanoma cure rate lower than 17% in five years.The most main method to cure is the traditional chemotherapy or radiotherapy or the tumor immune targeted therapy. Radiotherapy and chemotherapy is the main method for the treatment of cancer.radiation and chemotherapy with low selectivity, toxicity, and kill both tumor cells and normal cells; The time of the development of tumor immune targeted therapy is short with shortcoming of short duration. Natural compounds have a natural, low toxicity, patients psychological acceptance of higher a variety of advantages.so, treating tumor or adjuvant postoperative rehabilitation from Chinese herbal medicine or plants are becoming more common.Through the screening of large amounts of natural compounds, we found that nobiletin and osthole can inhibit the proliferation and migration of melanoma. This thesis is divided into three parts.the first part introduces melanoma, the mechanism and treatment of melanoma.The second part proved nobiletin and osthole can inhibit the proliferation and migration of melanoma at a cellular level; B16F10 melanoma cells in mice and A375 human melanoma cells has obvious inhibiting effect of cell proliferation by the use of the MTS and cloning method. Nobiletin and osthole can significantly inhibit melanoma cell migration by wound healing and transwell experiments. In the molecular mechanism, nobiletin and osthole can affect the Wnt signaling pathways to regulate downstream signal factor, Nobiletin weaken snail and twist to influence the expression of N-cadherin, E-cadherin to slow down the cell migration by adjusting Wnt signaling pathways downstream; osthole weaken slug to influence the expression of N-cadherin, E-cadherin to slow down the cell migration. On the molecular mechanism of proliferation inhibition of melanoma, nobiletin and osthole were affect downstream cyclinD1 through Wnt signaling pathways regulating cell cycle to inhibit melanoma cell proliferation. The third part of the animal level that nobiletin and osthole inhibit the growth of melanoma and lung metastasis.Through the subcutaneous tumorburdened experiment found that both nobiletin and osthole has a significant inhibitory effect on the growth of melanoma. Through tail vein injection of pulmonary metastasis of melanoma,we know that nobiletin and osthole can obviously reduce the transfer of melanoma in the lungs, lung tumor number decreasing significantly compared with control group showed the effect of the drugs.