Article Text
Abstract
Introduction Endometrial cancer is the most common gynecologic cancer in the United States. Hormonal therapy with megestrol acetate is used in fertility-sparing therapy or treatment of recurrent or metastatic disease, but efficacy has been limited. We assessed the effect of combining megestrol acetate with baicalein, a natural flavone shown to inhibit endometrial cancer cell growth.
Methods Human endometrial cancer cell lines, HEC-1A and ECC-1, were treated with baicalein or megestrol either alone or in combination at various concentrations. Cell viability was determined after 72 hours. Cell lysates were analyzed for expression of signaling molecules involved in cell growth and survival by Western blot. Mice were inoculated in the flank with HEC-1A cells, then randomized into treatment groups of vehicle control, baicalein, megestrol, and combination of baicalein and megestrol. Tumor volume was assessed with calipers.
Results Combination of megestrol acetate with baicalein resulted in a synergistic anti-proliferative effect in both endometrial cancer cells, and significantly reduced tumor growth in a HEC-1A xenograft endometrial cancer mouse model. The observed growth inhibition with baicalein was associated with decreased levels of pS6K1, pMAPK, pSTAT3, BCL-2, BCL-XL, CDK4 and cyclin D in HEC-1A cell.
Conclusion/Implications Anti-tumor activity of megestrol acetate can be enhanced by combining with baicalein both in vitro and in vivo, suggesting a potential application of baicalein as a therapeutic adjunct for the treatment of endometrial cancer.