Inhibition Of Resveratrol On HCV Related HCC Carcinogenesis

BackgroundLiver cancer is a severe disease worldwide. It is famous for its lethality rate andmetastasis. The carcinogenesis of liver cancer involves quite a lot of signaling pathways.Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Hepatitis CVirus is one of the most important causes of HCC and become a hot topic in scientificfield. Hepatosteatosis is a major pathological feature of HCV infection. Clinical researchshows that the incidence of HCC is higher in the patients with hepatosteatosis. Steatosis isan independent risk factor of HCC, which draw more attention of the world. Therefore, theway to treat hepatosteatosis becomes an urgent problem of the hepatocarcinoma therapy.HCV CORE protein can trigger the carcinogenesis of HCC in mice and produce thesame pathological features as chronic HCV infection. HCV CORE protein can directlyinduce hepatosteatosis, which means HCV CORE protein may have the capacity ofdevelop HCC. At the same time, mitochondrial dysfunction and chronic inflammation mayalso happen in the HCV CORE protein models. HCV CORE protein models have already become reasonable models of HCV infection.Resveratrol have a bunch of function, such as anti-inflammation, antioxidant andanticancer. It is derive from plants. There is no significant side effect in resveratrol asreported. Study shows that, it has an obvious therapeutic effect on nonalcoholic fatty liverdisease. It is shown to have function on variety tumors. It enhances the effect ofchemotherapy in cancer patients.Resveratrol is a Sirt1(silent mating type information regulation2homolog-1)activator, which can increase the expression of SIRT1. SIRT1expression is decreased inHCV CORE related steatosis. Therefore, resveratrol may figure out how to prevent thecarcinogenesis of HCC and how to prolong the longevity of the patients.ObjectsThis project is designed to find the function of resveratrol on HCC carcinogenesis.Experiments were also designed to find out whether resveratrol can inhibit the growth ofHCC after HCV infection. Our purpose on this project is to find new medicine for HCCprevention and treatment.Methods1. Resveratrol function on precancerous lesions after HCV infection.(1) We infect the hepatocyte in vivo and in vitro. At the meantime, we useresveratrolto treat the mice or the cells. After48h treatment，HE staining andOil red O staining are all used to detect the lipid level in the hepatocyte.Realtime PCR and Western blot are used to detect the gene expression andprotein expression level.(2) Seahorse machine was to detect the mitochondrial dysfunction, and then findthe way resveratrol used to regulate the mitochondrion.2. Resveratrol function on hepatocarcinoma in its carcingenesis(1) HCV CORE adenoviruses were used to infect the mice. Then, we inject thehepatocarcinoma cell directly into the liver. Resveratrol treatment is given tothe mice. Then we detect the cell growth in the liver, and study themechanism.(2) Investigate whether resveratrol has an effect on HCC cell growth, invasionand migration. Find out whether resveratrol has an effect on chronic inflammation and mitochondrial dysfunction after HCC developed.Results:1. Resveratrol can inhibite the precancerous lesion HCC in chronic HCV infection invivo. These lesions include steatosis, chronic inflammation, and mitochondrialdysfunction and so on. Resvratrol may regulate the moleculars in lipid metabolism.It can dramatically inhibit hepatosteatosis.2. Resveratrol also may regulate mitochondrial function at HCV CORE infection invitro. It can increase the oxidative respiratory. Resveratrol also can inhibit theactivation of Nuclear Factor Kappa B（NF-kB）, decrease inflammation.3. Reseratrol can inhibit HCC cell growth after it occurrence in vivo. Although thereare different pathways before and after HCC occurrence, resveratrol may regulatelipid metabolism and protect the mitochondrion.4. Resveratrol could inhibit HCC cell growth and metastasis. Transwell assay, woundhealing assay and MTT assay （3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide assay）were used in this part. Resveratrol can inhibitNF-Kb signaling pathway activation when HCV CORE adenovirus infectionhappened in HCC cells. The mechamism also can be the crosstalk between NF-kBand Sirt1pathway.ConclusionResveratrol, as an activator of Sirt1gene, is a multifunctional medicine，it hasmultiple targets. It may have promising effects on anticancer. Resveratrol may work withmany signailing pathways during carcinogenesis of HCC. Many precancerous lesionswere inhibits after resveratrol treatment. Hepatocarcinoma cell growth and metastasiswere inhibited by resveratrol. Different microenvironments stimulate different geneexpression. Resveratrol plays different roles in cancer treatment and research is badlyneeded.