Study On The Effects Of Fucoidan On Cell Proliferation And Apoptosis In Human Hepatoma Carcinoma Cell And Its Mechanism

Liver cancer is one of the most common malignant tumor s, which is called the biggest killer of human health in the new century, and it is one of the six most common cancers in the world. In our country, the proportion of patients with liver cancer had been increasing year by year. Recently, the clinical surgery methods commonly used, such as surgical therapy and chemical and radioative therapy can cause bone marrow suppression, low immunity or other toxic and side effects. In addition, the cancer cells themselves can reduce cell drug intake or drug activity to make cells resistant to drugs. Therefore, we need to find and develop new anti-cancer drugs with low toxicity and high efficiency.Because of its unique marine ecological environment, the ocean produces all kinds of biological resources and numerous kinds of biological species, which contain a variety of novel compounds having special chemical structure, mutipule pharmacological and biological activities. A substantial number of investigations repot that Fucoidan is one of the most important marine bioactive polysaccharides which can resisit inflammation and tumor. However, none of them report what its detail mechanism on the treatment of liver cancers is. Accordingly, this paper detects the anti-cancer effects of Fucoidan, on the basis of wich systematicly studys about its anti-cancer mechanism. All the results show as follows.1) Fucoidan can effectively inhibit the cell HepG2 proliferation. The liver cancer cell HepG2, lung cancer cells A549 and normal liver cells L02 was treated by d ifferent concentrations of Fucoidan for 24 h. MTT detecting result shows that Fucoidan can inhibit HepG2 and lung cancer cells A549 proliferation in the concentration dependent way, but does not affect the growth and proliferation of the normal liver cells. The inhibitory effects of Fucoidn on cancer cells are different, so we need to use different concentration Fucoidan to treat different kinds of tumers.2) Fucoidan can arrest the cell cycle of HepG2 and induce apoptosis. Treating HepG2 cells with different kinds' concentrations of Fucoidan for 24 h, by PI staining and periodic flow cytometry detecting, we find that with the Fucoidan concentration increasing, more and more cells stay in G2/M phase, which indicate that Fucidan can arrest HepG2 cells in G2/M phase. In addition, treating HepG2 cells with 4mg/mL Fucoidan for 24 h, the Hoechst staining results show that Hep G2 can exhibit morphological features' change associated with apoptosis. Further using double staining method and flow cytometry detecting, we find that Fucoidan could induce Hep G2's apoptosis in a concentration dependent way.3) Fucoidan can reglulate the transcription of cell cycle related protein to arrest cell cycle, and regulate the transcription and trslation of apoptosis related protein to induce cell apoptosis. RT-PCR results show that Fucoidan can reduce the transcription of cycle protein kinase CDK1 and CDK2, inhibit the activaty of Cyclins, thus the nomal cell cycle is arrested. Therefor, Fucoidan can inhibit the cell mitosis process. In addition, Fucoidan can also promote hepatoma cells apoptosis by inhibiting the transcription of anti-apoptosis gene Bcl-2, and activating the transcription of Bax and p53. Besides, Western blot results furtherly show that Fucoidan can induce cell apoptosis by inhibiting the activation of Bcl-2 expression, and activating the transcription and trslation of Bax and p53.This article results show that Fucoidan can significantly inhibit hepatoma carcinoma cells proliferation by activating the mitochondrial dependent endogenous apoptotic pathway and arresting cell cycle.