The Inhibition Effect of Triptolide on Human Endometrial Carcinoma Cell Line HEC-1B: a in vitro and in vivo Studies

Abstract

<b>Background:</b> To investigate the inhibitory effect and the underlying mechanism of triptolide on culturedhuman endometrial carcinoma HEC-1B cells and corresponding xenograft. Materials and <br/><b>Methods</b>: For in vitrostudies, the inhibition effect of proliferation on HEC-1B cell by triptolide was determined by MTT assay; cellcycle and apoptosis of the triptolide-treated and untreated cells were detected by flow cytometry. For in vivostudies, a xenograft tumor model of human endometrial carcinoma was established using HEC-1B cells, thenthe tumor-bearing mice were treated with high, medium, and low-dose (8 μg, 4 μg and 2 μg/day) triptolide orcisplatin at 40 μg/day or normal saline as control. The mice were treated for 10-15 days, during which body weightof the mice and volume of the xenograft were weighted. Then expression of Bcl-2 and vascular endothelial growthfactor (VEGF) was analyzed by SABC immunohistochemistry. <br/><b>Results</b>: Cell growth was significantly inhibitedby triptolide as observed by an inverted phase contrast microscope; the results of MTT assay indicated thattriptolide inhibits HEC-1B cell proliferation in a dose and time-dependent manner; flow cytometry showed thatlow concentration (5 ng/ml) of triptolide induces cell cycle arrest of HEC-1B cells mainly at S phase, while higherconcentration (40 or 80 ng/ml) induced cell cycle arrest of HEC-1B cells mainly at G2/M phase, and apoptosisof the cells was also induced. High-dose triptolide showed a similar tumor-inhibitory effect as cisplatin (-50%);high-dose triptolide significantly inhibited Bcl-2 and VEGF expression in the xenograft model compared tonormal saline control (P<0.05). <br/><b>Conclusions</b>: triptolide inhibits HEC-1B cell growth both in vitro and in mousexenograft model. Cell cycle of the tumor cells was arrested at S and G2/M phase, and the mechanism may involveinduction of tumor cell apoptosis and inhibition of tumor angiogenesis.