Antiproliferative effects of 2-methoxyestradiol alone and in combination with chemotherapeutic agents on human endometrial cancer cells

Objective: 2-methoxyestradiol (2-ME), an endogenous estradiol metabolite, has potent antiproliferative effects on cancer cells. However, its usefulness for treating endometrial cancer has not yet been fully explored. We investigated for the first time whether in vitro combinations of 2-ME with various chemotherapeutic agents might result in a synergistic inhibitory effect on the proliferation of human endometrial cancer cells. Methods: As a model, two different human endometrial cancer cell lines, HEC-1-A and RL95-2, were used. These cells were treated with 2-ME alone or in combination with paclitaxel, cisplatin, or doxorubicin. Measurements to detect an antiproliferative effect were performed after 24, 48, and 72 hours using the MTT assays. Results: In both endometrial cancer cell lines a significant synergistic effect of 2-ME with paclitaxel was observed. The combination of 2-ME and cisplatin was not synergistic and provided only additive effects. The antiproliferative effect of 2-ME was somewhat antagonized by doxorubicin. Conclusions: Our study shows that 2-ME has a direct antiproliferative effect on endometrial cancer cells. Our results also show a potential anticancer synergy between 2-ME and paclitaxel in vitro. On the other hand, no remarkable synergistic actions were observed between 2-ME and doxorubicin, suggesting that 2-ME may selectively enhance the anticancer actions of certain chemotherapeutic agents in human endometrial cancer. Therefore, combination therapy should be investigated further as an additional therapeutic option for advanced or recurrent endometrial cancer.