OncoTargets and Therapy (Apr 2016)
Vitamin D postpones the progression of epithelial ovarian cancer induced by 7, 12-dimethylbenz [a] anthracene both in vitro and in vivo
Abstract
Lizhi Liu,1,* Zhiyong Hu,2,* Hemei Zhang,3 Yongfeng Hou,1 Zengli Zhang,4 Guangming Zhou,5 Bingyan Li1,5 1School of Public Health, Medical College of Soochow University, Suzhou, 2Department of Chronic Disease Management, Lishui Center for Disease Control and Prevention, Lishui, 3Department of Chronic Disease Management, Wenzhou Center for Disease Control and Prevention, Wenzhou, 4Department of Labor Hygiene and Environmental Health, School of Public Health, Soochow University, Suzhou, 5School of Radiation Medicine and Protection, Soochow University, Suzhou, People’s Republic of China *These authors contributed equally to this work Purpose: Ovarian cancer is the most lethal malignancy of the female reproductive system, and the prevention and treatment of ovarian carcinoma are still far from optimal. Epidemiological studies reported that ovarian cancer risk was inversely associated with low level of 25-hydroxy vitamin D [25(OH)]. Therefore, this study focuses on exploring the chemoprevention of vitamin D on epithelial ovarian cancer induced by 7, 12-dimethylbenz [a] anthracene (DMBA).Methods: The mouse ovarian surface epithelial cells were isolated from estrus mice by mild trypsinization and maintained in completed culture medium by repeated passaging. The malignant transformation of mouse ovarian surface epithelial cells was induced by DMBA in vitro. DMBA was directly injected into the bursa of mouse ovary to produce optimized in vivo ovarian cancer model.Results: The results indicate that 1α,25 dihydroxyvitamin D3 may delay malignant transformation of mouse ovarian surface epithelial cells induced by DMBA and significantly decreased the colony formation rate from 18.4% to 3.2% (P<0.05). There was a negative correlation between incidence of DMBA-induced tumor and 25-hydroxy vitamin D level (R2=0.978, P<0.05). Vitamin D3 can delay the progression of ovarian cancer induced by DMBA, and the administration of vitamin D3 during the whole process worked more effectively than the administration only during tumor initiation or promotion. Moreover, we found the vitamin D3 increased the expression of E-cadherin and vitamin D receptor while it decreased the expression of β-catenin.Conclusion: We succeeded in establishment of epithelial ovarian cancer models both in vitro and in vivo. The DMBA-implanted model in mice yields high incidence and specificity of epithelial derived tumors. We also found that vitamin D delays the progression of ovarian cancer. However, spontaneous epithelial ovarian carcinoma models are still to be explored for testing the preventive effects of vitamin D on epithelial ovarian cancer. Keywords: vitamin D, epithelial ovarian cancer, DMBA, experimental animal model, chemoprevention, vitamin D receptor
