In vitro model of normal, immortalized ovarian surface epithelial and ovarian cancer cells for chemoprevention of ovarian cancer.
In vitro model of normal, immortalized ovarian surface epithelial and ovarian cancer cells for chemoprevention of ovarian cancer.
复制标题
用于卵巢癌化学预防的正常永生化卵巢表面上皮细胞和卵巢癌细胞的体外模型。
DOI：
10.1016/j.ygyno.2005.01.051
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Zou,Changping
中科院分区：
文献类型：
--
作者：
Brewer,Molly;Wharton,JTaylor;Wang,Jian;McWatters,Amanda;Auersperg,Nelly;Gershenson,David;Bast,Robert;Zou,Changping
BACKGROUNDEpithelial ovarian cancer has the highest mortality rate among the gynecologic cancers. The synthetic retinoid, N-(4-hydroxyphenyl) retinamide (4-HPR), has been used in the chemoprevention of ovarian cancer. However, the effectiveness of its application for different populations has been questioned because of the genetic differences among normal, high risk, and women with cancer.OBJECTIVETo explore the similarities and the differences in 4-HPR effects on different ovarian epithelial cells which mimic different populations of women, normal ovarian surface epithelium to represent the normal population of women, immortalized ovarian surface epithelium to represent premalignant changes, and cells derived from ovarian cancer cells to represent malignant changes were used as in vitro models.METHODSNormal ovarian surface epithelial cells, immortalized ovarian surface epithelial cells, and ovarian cancer cells were incubated for different intervals with increasing concentrations of 4-HPR. Growth inhibition, the fraction of apoptotic cells, the expression of apoptosis-related genes, including p53, p16, p21, and caspase-3, and mitochondrial permeability transition were measured before and after 4-HPR treatment.RESULTSTreatment with 4-HPR produced growth inhibition and apoptosis in a dose-dependent manner for all 3 cell types. 4-HPR produced the strongest activation of the p53 pathway in normal ovarian epithelial (NOE) cells, while it caused the largest increase in MPT in the cancer cells, suggesting a different mechanism for growth inhibition and/or apoptosis in these cell lines. 4-HPR, at a concentration of 10 μM, had a maximal effect on caspase-3 activity at 72 h in normal cells and at 48 h in immortalized and cancer cells, although the effects were modest.CONCLUSIONSNormal ovarian surface epithelial cells, immortalized ovarian surface epithelial cells, and ovarian cancer cells showed a differential response to 4-HPR. Although the same endpoints of growth inhibition and apoptosis induction were present in response to 4-HPR, these endpoints may be regulated through different pathways.IMPLICATIONSClinical trials with higher concentrations of 4-HPR should prove beneficial.
