Study On The Mechanism That Icaritin Inhibits Proliferation Of HepG2Cells

Hepatocellular carcinoma (HCC) is one of the most common malignant tumorsworldwide. China is the hardest hit of liver cancer, and the highest mortality of livercancer is happened in China.Therefore study on the treatments and drugs to liver cancer isof great significance in China. Epimedium Genus which has long been used in Chinesetraditional medicine has many pharmacological activities such as enhancement ofosteoblastic and cardiac differentiation. Icaritin, a prenylflavonoid derivative from theChinese herb Epimedium, possesses various activities, including cardiovascular protection,osteoblastic enhancement, the immune system regulation, as well as inhibition of humancancer cells growth. However, the function and the underlying mechanisms of icaritinrestrainment on cell growth have not been well discovered. In this study, we used HepG2cell line, a kind of human hepatocellular carcinoma cell line, as test material, in order toexplain the aititumor mechanism of icaritin by using the molecular biology methods suchas MTT, RT-PCR and Western blot. The results are as follows:(1) Icaritin inhibited the proliferation of human HepG2cell in the doses and timedependent ways. MTT assay showed that the higher the drug concentration, the strongerthe inhibition on cell growth, which means that icaritin inhibits the proliferation of cancercells in a dose-dependent manner.(2) Icaritin induced S arrest in cell cycle progression. HepG2cells were treated withicaritin of gradient concentrations for24h, Cell cycle analysis by flow cytometry, showedthat icaritin induced an obvious S arrest. Icaritin treatment down-regulated the expressionlevels of cyclin A and CKD2which were the key genes of S phase. Expression assay ofp53and p21by Western blot analysis showed that icaritin induced apoptosis of HepG2Cells.(3) The mechanism of icaritin inhibition on HepG2cell growth is to inhibit theexcessive activation of p-JAK2and p-STAT3. mRNA levels of JAK2and STAT3weredetected with RT-PCR, and the expression levels of p-JAK2and p-STAT3were assayed byWestern blot.The results showed that icaritin treatment down-regulated mRNA levels ofJAK2and STAT3and inhibited the activation of p-JAK2and p-STAT3.It means that icaritin inhibits the proliferation of HepG2cells through curbing the excessive activationof JAK2/STAT3signaling pathway.Through this study we found that icaritin has significant inhibitive effect on HepG2cells, which may provide a new way for the development of new effective drugs on livercancer.