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目的探讨雌激素受体与卵巢癌SKOV3细胞顺铂耐药的相关性。方法将4×106个SKOV3细胞接种于30只裸鼠大腿皮下构建人卵巢癌细胞系SKOV3异种移植瘤模型,并随机分为对照组15只和实验组15只。对照组予以0.9%Na Cl,每周1次,共给药5次,腹腔注射;实验组予以顺铂20 mg·kg~(-1),每周1次,共给药5次,腹腔注射。再从对照组和实验组上获得卵巢癌移植瘤SKOV3细胞。用免疫细胞化学法和流式细胞术检测SKOV3细胞中雌激素受体的表达水平;用噻唑蓝(MTT)法和流式细胞术分别检测不同浓度顺铂(0,1,5,10,15,20μg·m L~(-1))和雌激素受体抑制药ICI182(0,1,5,10,20μmol·L~(-1))单独及联合应用对SKOV3细胞的增殖及凋亡的影响。结果实验组和对照组的免疫细胞化学评分(HIS值)分别为(10.04±2.93),(6.73±2.37)分;雌激素受体表达分别为231.39±15.33,205.81±12.50,差异均有统计学意义(P<0.01)。ICI182对对照组、实验组细胞均表现为增殖抑制,呈现剂量-时间依赖关系;随着顺铂浓度的升高,10μmol·L~(-1)ICI182联合顺铂作用SKOV3细胞时抑制作用显著增强,差异有统计学意义(P<0.01)。实验组和对照组分别用10μmol·L~(-1)ICI182+10μg·m L~(-1)顺铂处理后,其细胞凋亡率分别为(70.07±0.64)%和(82.13±0.87)%,差异有统计学意义(P<0.01)。结论雌激素受体参与了化疗耐药过程,通过ICI182抑制雌激素受体蛋白可能逆转卵巢癌细胞的顺铂耐药。
Objective To investigate the relationship between estrogen receptor and cisplatin resistance in ovarian cancer SKOV3 cells. Methods 4 × 106 SKOV3 cells were inoculated subcutaneously in the thighs of 30 nude mice to construct a human ovarian cancer cell line SKOV3 xenograft model and randomly divided into control group 15 and experimental group 15. The control group was treated with 0.9% NaCl once a week for 5 times and intraperitoneally; the experimental group was given cisplatin 20 mg · kg -1 once a week for 5 times, . Ovarian cancer xenografts SKOV3 cells were obtained from the control group and the experimental group. Immunocytochemistry and flow cytometry were used to detect the expression of estrogen receptor in SKOV3 cells. MTT assay and flow cytometry were used to detect the levels of cisplatin (0, 1, 5, 10, 15) , 20μg · m L -1) and estrogen receptor inhibitor ICI182 (0, 1, 5, 10, 20μmol·L -1) alone and in combination on SKOV3 cell proliferation and apoptosis influences. Results The immunocytochemistry scores (HIS) of the experimental group and the control group were (10.04 ± 2.93) and (6.73 ± 2.37) points respectively; the expressions of estrogen receptor were 231.39 ± 15.33 and 205.81 ± 12.50, respectively, with statistical difference Significance (P <0.01). ICI182 showed inhibition of proliferation in control and experimental groups in a time-and dose-dependent manner. With the increase of cisplatin concentration, the inhibitory effect of ICI182 combined with cisplatin on SKOV3 cells was significantly enhanced by 10μmol·L -1 ICI182 , The difference was statistically significant (P <0.01). The apoptosis rates of the experimental group and the control group treated with 10μmol·L -1 ICI182 + 10μg · m L -1 cisplatin were (70.07 ± 0.64)% and (82.13 ± 0.87) %, The difference was statistically significant (P <0.01). Conclusion The estrogen receptor is involved in the chemoresistance process. Inhibition of estrogen receptor protein by ICI182 may reverse cisplatin resistance in ovarian cancer cells.