Growth regulation of epithelial ovarian cancer cell lines by female sex hormones = 여성 호르몬에 의한 상피성 난소암 세포주의 성장 조절
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- Growth regulation of epithelial ovarian cancer cell lines by female sex hormones = 여성 호르몬에 의한 상피성 난소암 세포주의 성장 조절
- D C Park; Yang Kyu Choi; J W Kim; J S Park; D H Kim; S E Namkoong; J M Lee
- Bibliographic Citation
- Korean Journal of Obstetrics and Gynecology, vol. 45, no. 3, pp. 408-415
- Publication Year
- Object : The effect of low dose estradiol used for respect of hormone replacement therapy on the proliferation of epithelial ovarian cancer was investigated in vitro and in vivo. Method : In vitro, 6 epithelial ovarian cancer cell lines containing different estrogen receptors were used: OVCAR-3, MDAH2774, PA-1, SK-OV-3 SNU-8, and ES-2 for XTT assay. The difference in the proliferation was compared among the group treated with FSH and LH (FL group), the group with FSH, LH and additionally estradiol (FLE group) and control group. Using flow cytometry, the changes in the cell cycle of the ephithelial ovarian cancer cell lines between the FL group and FLE group were analyzed. In vivo, OVCAR-3 was xenografted in female NOD-SCID mice, which had both ovaries removed, to compare the extent of proliferation of the xenograft tumor between the FL group and FLE group. The difference in proliferation was confirmed in the xenograft tumor tissues through the immunohistochemical staining for PCNA and p53. The expressions of the proteins-Rb, p16, cyclin D1, which controls cell cycle progression from G1 to S phase were examined by Western blot to investigate the mechanism behind the arrest at the G0/G1 phase. Results : In vitro, the difference of proliferation in FLE group compared to the FL group was not statistically significant (P>0.05). In flow cytometric assay, FL group showed a tendency to distribute the cell cycle to the S phase, compared to the control group, and the addition of estradiol tended to arrest the cell cycle at the G0/G1 phase, compared with FL group. In vivo, the proliferation of xenograft tumor was suppressed in FLE group, compared with the FL group (P<0.05). The immunohistochemical staining for PCNA, was more frequently and strongly expressed in FL group than in FLE group. But for p53, it was too weakly expressed to compared. In addition, the expression of Rb protein was stronger in FLE group than in FL group. On the other hand, cyclin D1 expression was significantly evident in FL group, while the expression of p16 was too weak to be compared. Conclusion : The results of this study show that estradiol does not promote the proliferation of epithelial ovarian cancer but rather decrease the proliferation that was promoted by FSH and LH during menopause; this may be due to the arrest of cell cycle at G0/G1 phase by estradiol.
- ovarian cancer; low dose of estradiol; FSH; LH
- South Korea
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