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目的研究百里醌对卵巢癌生长的影响及其作用机制。方法百里醌作用卵巢癌细胞株SKOV3后,CCK-8法检测细胞增殖;ELISA法检测细胞凋亡;荧光探针法检测细胞内活性氧(ROS)水平;Western blotting检测胞核蛋白Nrf2、胞浆蛋白Keap1、Akt、p-Akt、NQO1、GCLC的表达;实时荧光定量PCR(RT-qPCR)检测细胞中NQO1和GCLC mRNA水平。制备裸鼠卵巢癌皮下移植瘤模型,观察百里醌对肿瘤生长的影响;免疫组化检测肿瘤组织Nrf2、NQO1和GCLC的阳性表达。结果与对照组比较,百里醌明显抑制SKOV3细胞生长(P<0.05、0.01),并诱导细胞凋亡(P<0.01);升高细胞内ROS水平(P<0.05);下调胞核Nrf2蛋白及胞浆p-Akt蛋白表达(P<0.05),上调Keap1蛋白表达(P<0.001);下调NQO1、GCLC的mRNA和蛋白表达(P<0.05、0.01)。百里醌抑制裸鼠卵巢癌皮下移植瘤的生长(P<0.01),降低肿瘤组织中Nrf2、NQO1、GCLC的阳性表达(P<0.05、0.01)。结论百里醌抑制卵巢癌生长,其机制可能是抑制胞核Nrt2蛋白表达,促进癌细胞内ROS的产生,诱导细胞凋亡。
Objective To study the effects of thioridone on the growth of ovarian cancer and its mechanism. Methods Cell proliferation was detected by CCK-8 assay after apoptosis of ovarian cancer SKOV3 cell line. Apoptosis was detected by ELISA. The level of reactive oxygen species (ROS) was detected by fluorescent probe. The expression of Nrf2, The expression of plasma proteins Keap1, Akt, p-Akt, NQO1 and GCLC were detected by real-time fluorescence quantitative PCR (RT-qPCR) The nude mouse model of ovarian cancer xenografts was established to observe the effect of thioridone on the tumor growth. Immunohistochemistry was used to detect the positive expression of Nrf2, NQO1 and GCLC. Results Compared with the control group, thymidine inhibited the growth of SKOV3 cells (P <0.05, 0.01) and induced the apoptosis of cells (P <0.01), increased the level of intracellular ROS (P <0.05), reduced the expression of Nrf2 protein (P <0.05), up-regulated the expression of Keap1 protein (P <0.001) and down-regulated the mRNA and protein expression of NQO1 and GCLC (P <0.05, 0.01). Thiolone inhibited the growth of subcutaneous xenograft tumors in nude mice (P <0.01), and decreased the expression of Nrf2, NQO1 and GCLC (P <0.05, 0.01). Conclusion Thymol inhibits the growth of ovarian cancer. The possible mechanism is that it inhibits the expression of Nrt2 protein, promotes the production of ROS in cancer cells and induces apoptosis.