4.Knockdown of CYP24A1 enhances the anti-invasion effect of 1α,25(OH)2D3 on mouse ovarian cancer cells by inhibiting EMT
徐继明 王萍 侯永凤 蒋菲 李冰燕
摘要：Increasing evidence has shown that epithelial-mesenchymal transition (EMT) can endow cancer cells with motile and invasive properties. In ovarian tissue, EMT not only plays a physiological role in the postovulatory repair of ovary surface epithelial (OSE) cells, but also an important role in the aggressiveness and recurrence of ovarian cancer. Previous research has indicated that 1α,25(OH)2D3 decreases the migration and invasion of many kinds of tumor cells by suppressing EMT. However, it remains unclear whether 1α,25(OH)2D3 can inhibit the process of EMT in mouse OSE (MOSE) cells at different stages of oncogenic transformation. In this study, we found that 1α,25(OH)2D3 significantly reduced the migration and invasion of late malignant transformed MOSE (M-L cells) cells by inhibiting EMT both in vitro and in vivo, but not in intermediate transformed (M-I) cells. Interestingly, the expression of CYP24A1 in M-I cells was distinctly higher than M-L cells following continuous treatment with 1α,25(OH)2D3. Furthermore, we demonstrated that the knockdown of CYP24A1 enhanced the anti-invasion properties of 1α,25(OH)2D3 on both M-I and M-L cells by upregulating the expression of E-cadherin, and downregulating the expression of N-cadherin, Vimentin, β-catenin and Snail. These findings imply that CYP24A1 is a potential target for the inhibition of EMT and ovarian cancer metastasis.