三氧化二砷联合多西他赛对人卵巢癌细胞株HO8910的抗肿瘤作用机制研究  

Study of mechanisms of anti-tumor aganist arsenic trioxide combined with docetaxel for human ovary cancer cell line HO8910

作　　者：车力凡[1] 王颖[2] 刘瑶[2] 

机构地区：[1]潍坊市益都中心医院医务处,山东潍坊262500 [2]潍坊市益都中心医院妇产科,山东潍坊262500

出　　处：《中国临床药理学杂志》2018年第2期145-147,共3页The Chinese Journal of Clinical Pharmacology

基　　金：潍坊市卫生局科研项目计划基金资助项目(2010017)

摘　　要：目的研究三氧化二砷联合多西他赛对体外培养卵巢癌细胞株的增殖及细胞凋亡的影响。方法将卵巢癌细胞随机分为4组:空白组(0.9%Na Cl)、模型组(8μmol·L^(-1)As2O3)、对照组(1 mg·L^(-1)多西他赛)和实验组(8μmol·L^(-1)As_2O_3+1 mg·L^(-1)多西他赛),4组均培养72 h。用噻唑蓝法检测药物对细胞生长的抑制率,用免疫印迹法和实时定量聚合酶链式反应检测药物作用后细胞蛋白激酶样R内质网激酶(PERK)、同源蛋白(CHOP)、细胞凋亡蛋白酶Caspase3与B淋巴细胞瘤-2(Bcl-2)的表达情况。结果药物干预72 h后,模型组、对照组与实验组的抑制率分别为(3.04±0.76)%,(14.91±1.52)%,(38.79±2.94)%。与模型组比较,对照组和实验组差异均有统计学意义(均P<0.01);与对照组比较,实验组差异也有统计学意义(P<0.01)。药物干预72 h后,模型组、对照组与实验组的PERK分别为6.27±0.18,6.28±0.19,7.74±0.90;这3组的CHOP分别为6.25±0.24,6.27±0.16,7.51±0.49;这3组的Caspase分别为37.14±0.21,37.21±0.63,9.40±0.33。与模型组比较,实验组差异均有统计学意义(均P<0.05);与对照组比较,实验组差异也均有统计学意义(均P<0.01)。结论 As_2O_3联合多西他赛可激活卵巢癌细胞株内质网应激效应,抑制卵巢癌细胞增殖,诱导卵巢癌细胞凋亡。Objective To investigate the effect of arsenic trioxide （As203 ） and docetaxel on cell proliferation and apoptosis of ovarian cancer cell line HO8910 in vitro. Methods The ovarian cancer cells were divided into blank group （ given 0. 9% NaC1 ）, model group （ 8 iμmol·L-1 As2 03 ） , control group （ 1μmol·L-1 docetaxel ） and experi- mental group （ 8 μmol·L-1 As2 O3 ± 1μmol·L-1docetaxel）. The 4 groups were cultured for 72 h. The inhibitory rate of drugs on cell growth was detected by MrIT. The expression of PKR - like ER kinase （ PERK）, C/EBP homologous protein（ CHOP）, Caspase 3 and B -cell lymphoma - 2 （Bcl - 2） were detected by Western blot. Results After the interven- tion of drugs for 72 h, the inhibition rates of ovarian cancer cells in model group, control group and experimental group were （3.04 ：t= 0. 76 ）%, （14. 91 ± 1.52）%, （38.79 ± 2.94）%. Compared with model group, the differences in experimental group and control group were statisticallysignificant （all P 〈 0. 01 ） ;compared with control group, the differences in experimental group were statistically signifi- cant （P 〈0. 01 ） . After 72 h of drug intervention, the PERK in model group, control group and experimental group were 6.27 ±0. 18,6.28 ±. 19,7.74 ± 0.90;the CHOP in above three groups were 6.25 ±0.24,6.27 ±. 16, 7.51 ±0. 49;the Caspase in above three groups were 37. 14 ±0. 21,37.21 ±0. 63,9. 40 ±0. 33. Compared with model group, the differences in experimental group were statistically significant （ all P 〈 0. 05 ） ; compared with control group, the differences in experimental group were statistically significant （ all P 〈 0.01 ） . Conclusion Arsenic trioxide com- bination with docetaxel can activate ER stress apoptosis channel on ovarian cancer cell lines, supress ovarian cancer cell proliferation and induce apoptosis in ovarian cancer cells.

关 键 词：三氧化二砷 多西他赛 卵巢癌细胞HO8910 凋亡蛋白 内质网 

分 类 号：R979.1[医药卫生—药品]