OBJECTIVE To explore the mechanism of oridon in（Ori）reversing the drug resistance of breast cancer cell MCF-7 to fulvestrant （Ful）. METHODS Ful-resistant breast cancer cell strains MCF- 7/Ful were induced and constructed in vitro . The relative cell viability of MCF- 7 cells and MCF- 7/Ful cells was detected by MTT assay ，inhibitory rate of Ori to MCF- 7/Ful cells was also detected. CompuSyn software was used to analyze the synergistic effect of Ori and Ful. MCF- 7/Ful cells were randomly divided into blank control group ，Ful group （5 μmol/L），Ori group （8 μmol/L），Ful（5 μmol/L）+Ori（8 μmol/L）group. The phosphorylation of phosphatidylinositol 3 kinase（PI3K）/protein kinase B （Akt）signaling pathway related protein in each group was detected by Western blot. MCF-7/Ful cells were used to prepare drug resistance model of transplanted tumor in nude mice，and they were randomly divided into blank control group ，Ful group （80 μmol/g），Ori group （50 μmol/g），Ful（80 μmol/g）+ Ori（50 μmol/g）group. The tumor weight and tumor inhibition rate were calculated ，to verify the reversal effect of Ori and Ful in vivo. RESULTS MTT assay showed that when Ful ≥10 μmol/L，the relative cell viability of MCF- 7/Ful cells was significantly higher than that of MCF- 7 cells（P＜0.05），and the drug resistance was significantly enhanced ；Ori had a significant inhibitory effect on MCF- 7/Ful cells ，the inhibition rate of Ori combined with Ful to MCF- 7/Ful cells was significantly increased （P＜0.05 or P＜0.01），and the effect of reversing drug resistance was significantly increased . The results of Western blot showed that compared with Ful group ，the phosphorylation levels of PI 3K and Akt protein in Ful+Ori group were significantly decreased （P＜0.05 or P＜ 0.01）. In vivo results showed that the tumor volume and mass of Ful+Ori group were significantly decreased ，and the tumor inhibition rate was （63.90±4.11）％，which was significantly higher than that of Ful group （P＜0.01）. CONCLUSIONS Ori can reverse drug resistance of breast cancer cell MCF- 7 to Ful ， and this effect may be through regulating PI 3K/Akt signaling pathway.

DNA methylation is a prevalent epigenetic modification in vertebrates, and it has been shown to be involved the regulation of gene expression and embryo development. However, it remains unclear how DNA methylation regulates sexual development, especially in species without sex chromosomes. To determine this, we utilized zebrafish to investigate DNA methylation reprogramming during juvenile germ cell development and adult female-to-male sex transition. We reveal that primordial germ cells (PGCs) undergo significant DNA methylation reprogramming during germ cell development, and the methylome of PGCs is reset to an oocyte/ovary-like pattern at 9 days post fertilization (9 dpf). When DNA methyltransferase (DNMT) activity in juveniles was blocked after 9 dpf, the zebrafish developed into females. We also show that Tet3 is involved in PGC development. Notably, we find that DNA methylome reprogramming during adult zebrafish sex transition is similar to the reprogramming during the sex differentiation from 9 dpf PGCs to sperm. Furthermore, inhibiting DNMT activity can prevent the female-to-male sex transition, sug-gesting that methylation reprogramming is required for zebrafish sex transition. In summary, DNA methylation plays important roles in zebrafish germ cell development and sexual plasticity.