EUGENOL SUPPRESSES THE DEVELOPMENT OF ESTROGEN RECEPTOR-POSITIVE PRECAN- CEROUS BREAST LESIONS AND REGULATES ESTROGEN RECEPTOR-RELATED PROTEINS

LIAO RUI^1,3, ZHANG GUIJUAN¹, BIE FENGJIE², MA MIN², MA YI⁴

¹the First Affiliated Hospital of Jinan University, Guangzhou, 510632, P. R. China - ²School of Traditional Chinese Medicine of Jinan University, Guangzhou, 510632, P. R. China - ³the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, P. R. China - ⁴Bio-Engineering institute of Jinan University, Guangzhou, 510632, P. R. China

Introdution: The breast precancerous lesions is a necessary stage of breast cancer, and most of drugs for the treatment of

breast precancerous lesions have a lot of adverse reactions, so finding a new drug effects on precancerous lesions of breast can-

cer has important significance. Eugenol has therapeutic effect on tumor，However, the mechanism of the treatment is not clear, the purpose of this study is to evaluate eugenol anti-tumor effect on ER positive precancerous lesions of breast cancer.

Material and methods: 40 female SD rats were randomized into 5 groups, 8 in each. The groups were named Blank control group, Model group, Tamoxifen group, The low dose of Eugenol cream group (0.5mg) and The high dose of Eugenol cream group (1mg) respectively. The rats with breast precancerous lesions were induced by 7,12-dimethylbenz(a)anthracene (DMBA) com- bined with estrogen and progesterone injection. Drug interventions by tamoxifen(TAM) ointment and Eugenol cream were also launched during the model formation. The rats were executed after 70d. In MCF-10AT cell lines, we use 180μM eugenol to treat the cell lines, then observed 24 hours. And then the correlated indexes are detected by Western-blot and elisa.

Results: 1mg eugenol significantly delayed the pathology process of rat breast tissue models in precancerous lesions of breast cancer, meanwhile, 1mg eugenol reduced the level of serum estradiol(E2) and the reduce rate was 36%, increased proges- terone(P) and the increase rate was 26%, in addition, the protein levels of ERα, GPER, p-AKT, GSK3-α, GSK3-β, p70s6k were decreased in the rat models and the decreased rates were respectively 31%, 53%, 57%, 58%, 56%, 93%, as well as MCF-10AT cell lines were treated with 180 μM eugenol, the decreased rates were respectively 35%, 60%, 63%, 57%, 42%, 68% (P < 0.01). However, in rat models the expressions of PTEN and ERβ protein were increased and the increase rates were 76%, 58% (P < 0.05), in MCF-10AT cell lines the increase rates of the expressions of PTEN and ERβ protein were 46%, 177%.

Discussion: eugenol is effective in the treatment of ER positive precancerous lesions of breast cancer, indicating that eugenol may be a new effective drug in treating ER positive precancerous lesions of breast cancer.