Epidermal growth factor's role on human hepatocellular carcinoma transplanted into nude mice

Abstract

Based on the results of in vivo and in vitro studies, EGF appears to be a hormonally regulated growth factor. In general, hormones have multiple modulatory activity according to concentration, and the hypothesis that a high cencentration of EGF is a negative growth factor has been proved in human carcinoma of esophagus and breast in vivo and in vitro studies. Some recent original papers shows that EGF can induce apoptosis in various cancer cells bv the mechanism of activation of STAT protein.This work was focused on clarifying the dose-dependent effects of epidermal growth factor on the growth, cell cycle, and ultra-structure of hepatocellular carcinoma. Human HCC SMMC-7721 was adopted to transplanted to the subcutaneous tissue of nude mice. 10 days After transplantaion, Human EGF(2ug and 10ug respectively) was injected locally into the subcutaneous tissue surrounding the tumor. After 4 weeks treatment, the tumor growth was evaluated by tumor volume, histologic examination; flow cytometric analysis of a cell cycle was performed after DNA staining with Propidium iodide (PI), and a morphological observation by electron microscope was done to qualify programmed cell death. The examination results showed a growth -inhibitory effect noted with 10ug of EGF, while not with 2ug of EGF. In the treated tumor, more apoptotic cells were counted, meanwhile cell cycle change characterized as the increase of S-phase fraction and the decrease of G01 and G2/M phase fraction. In conclusion, EGF shows its multiple modulatory activity in human HCC in vivo, and it can change the cell cycle and induce the apoptosis of HCC cells in uncertain path.We present the probably mechanism, that EGF induced apoptosis is closely related to great change of cell cycle fraction after the treatment of EGF.