米非司酮配伍顺铂对卵巢癌耐药细胞株CAOV_3/DDP细胞凋亡和性激素受体的影响

Effects of mifepristone and cisplatin on apoptosis and hormonal receptors in chemoresistant ovarian cancer cell lines CAOV_3/DDP

目的探讨米非司酮配伍顺铂对卵巢癌耐药细胞株CAOV3/DDP增敏作用以及凋亡率、雌激素受体(ER)和孕激素受体(PR)的影响。方法采用RPMI1640培养液对CAOV3/DDP细胞株进行培养,将CAOV3/DDP细胞株分5组:对照组(不加任何药物)、顺铂组(2μg/ml)、高剂量米非司酮加顺铂组(15μg/ml米非司酮和2μg/ml顺铂)、中剂量米非司酮加顺铂组(10μg/ml米非司酮和2μg/ml顺铂)、低剂量米非司酮加顺铂组(5μg/ml米非司酮和2μg/ml顺铂)。培养结束后采用MTT法观察不同浓度的米非司酮配伍顺铂对CAOV3/DDP细胞株增殖活力的影响;采用流式细胞术观察不同浓度的米非司酮配伍顺铂对CAOV3/DDP细胞株凋亡率、ER、PR的影响。结果与对照组比较,顺铂组对细胞增殖活力、细胞凋亡率以及ER、PR阳性率的影响,差异均无统计学意义(P>0.05);与顺铂组比较,各剂量米非司酮加顺铂组对细胞增殖活力、生存率以及细胞凋亡率、PR阳性率的影响,差异均有统计学意义(P<0.05,P<0.01),且随着米非司酮浓度的升高,对CAOV3/DDP细胞抑制作用逐渐增强,细胞凋亡率显著上升,PR阳性率下降(P<0.05,P<0.01),各组ER阳性率无统计学意义(P>0.05)。结论米非司酮联合顺铂对CAOV3/DDP细胞增殖活力均具有显著抑制作用,且与米非司酮的浓度呈剂量依赖关系,米非司酮可提高顺铂化疗的敏感性,其增敏作用与抑制孕激素分泌,促进卵巢癌细胞凋亡有关。

Objective To study the effects of mifepristone and cisplatin （DDP） on cell proliferation, apoptosis, estrogen receptor （ER） and progesterone receptor （PR） in chemoresistant ovarian cancer cell lines CAOV3/DDP. Methods CAOV3/DDP cells were cultured by RPMI1640 medium, and treated with different doses of medications： control group （without medication）, DDP group （2 μg/ml）, high-dose mifepristone combined with DDP group （15μg/ml mifepristone and 2 μg/ml DDP）, medium-dose mifepristone combined with DDP group（ 10μg/ml mifepristone and 2μg/ml DDP） and low-dose mifepristone combined with DDP group（5μg/ml mifepristone and 2 μg/ml DDP）. Cell proliferation activity, apoptosis, ER and PR were evaluated by MTT method, FCM respectively. Results Compared with control group, the cell proliferation activity, apoptosis rate, ER and PR in DDP group and low-dose mifepristone group have no statistical significance （ P 〉 0.05）. Compared with DDP group, cell proliferation activity, apoptosis rate, expression of ER and PR in each group of mifepristone combined with DDP have statistical significance （ P 〈 0.05 or P 〈 0.01） , Cell cyto-inhibition and apoptosis rate were increased gradually with the increase of mifepristone concentration, while PR decreased. The expression of ER in each group has no statistical significance （ P 〉 0.05）. Conclusion Mifepristone combined with DDP can induce cyto-inhibition in a concentration dependent manner in ovarian cancer CAOV3/DDP ceils, suggesting that mifepristone could obviously increase the chemosensitivity of DDP by inhibiting PR and increasing apoptosos.