ZHIBAI DIHUANG WAN CONTRIBUTES APOPTOSIS OF TUMOR CELLS IN ESTROGEN-RECEPTOR-POSITIVE BREAST CANCER MICE VIA ERK/AKT PATHWAY

YuLin Li¹, Wentao Si^{1, *}, Aihua Hou¹, Hongmin Shao¹, Rongrong Hu¹, Wen Wang¹, Yufei Yang²

¹Oncology Department, Yantai Traditional Chinese Medicine Hospital, Yantai, China - ²Oncology Department, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China

Background: As an important Chinese medicine, Zhibai Dihuang Wan (ZDW) has been used in clinical treatment. In this study, we aimed to investigate the potential mechanism of ZDW in the treatment of estrogen receptor-breast cancer. 

Methods: The transplanted tumor was established by subcutaneous injection of MCF-7 cells. Forty BALB/c nude mice were randomly divided into model, tamoxifen citrate (TAM, 2.5 mg/kg), ZDW (10 mg/kg), and TAM+ZDW groups. The levels of serum estradiol were measured by ELISA kit. Tumor weight and tumor inhibition rate in each group were monitored. Moreover, histopathological observation of tumors was observed by hematoxylin eosin (HE) and the expression of ERα, Bcl-2 and Bax in tumors was measured by immunohistochemical staining. The levels of ERα, p-ERK1/2, ERK1/2, p-AKT and AKTprotein in cancer tissues were analyzed by western blot.

Results: The inhibition rate of tumor in TAM + ZDW group was the highest among groups. HE staining revealed that the tumor cells in TAM, ZDW and TAM + ZDW group showed a reduction in mitosis together with cell morphology atrophy when compared to the model group. Meanwhile, after treatment of TAM or ZDW, the positive reactions of ERα and Bcl-2 were weaker. In TAM + ZDW group, the expressions of ERα and Bcl-2 were the lowest. The levels of ERα, and p-ERK1/2/ ERK1/2 protein in TAM, ZDW and TAM + ZDW groups were notably declined than those in model group (P<0.05). Moreover, compared with the model group, the expressions of p-AKT/AKT in TAM, ZDW and TAM + ZDW group were significantly higher (P<0.05).

Conclusions: ZDW could inhibit the growth of tumor and promote tumor celss apoptosis via adjusting ERK/AKT pathway in estrogen-receptor-positive breast cancer.