【摘要】：目的探討多巴胺受體阻斷劑硫利達(dá)嗪(thioridazine)對(duì)卵巢癌細(xì)胞株SKOV3、A2780增殖、凋亡的影響及其可能的作用機(jī)制。方法用不同濃度硫利達(dá)嗪(0、5、10、15、20μmol/L)作用SKOV3、A2780細(xì)胞,CCK8法檢測(cè)細(xì)胞增殖,流式細(xì)胞儀及DAPI染色檢測(cè)細(xì)胞凋亡,DCFH-DA法染色檢測(cè)ROS水平,彗星實(shí)驗(yàn)觀察細(xì)胞核DNA損傷情況,JC-1染色檢測(cè)線粒體膜電位變化,Western blot檢測(cè)P53、Bax、Bcl-2、細(xì)胞色素C、active Caspase-3蛋白的表達(dá)。結(jié)果硫利達(dá)嗪可抑制人卵巢癌細(xì)胞SKOV3、A2780的增殖,呈一定的劑量效應(yīng)關(guān)系(P0.05),濃度為15μmol/L時(shí),可產(chǎn)生明顯增殖抑制效應(yīng);流式細(xì)胞儀檢測(cè)顯示處理組(15μmol/L硫利達(dá)嗪作用24 h)凋亡率明顯高于對(duì)照組(P0.05);DAPI染色結(jié)果:處理組出現(xiàn)明顯細(xì)胞核固縮、碎裂及凋亡小體;DCFH-DA染色處理組ROS水平升高(P0.05);彗星實(shí)驗(yàn)結(jié)果提示處理組出現(xiàn)明顯的DNA損傷;JC-1染色發(fā)現(xiàn)處理組線粒體膜電位較對(duì)照組下降(P0.05);Western blot實(shí)驗(yàn)發(fā)現(xiàn)處理組P53、Bax、胞質(zhì)細(xì)胞色素C、active Caspase-3表達(dá)上調(diào),Bcl-2、線粒體細(xì)胞色素C表達(dá)下調(diào)。結(jié)論硫利達(dá)嗪可能通過(guò)誘導(dǎo)細(xì)胞內(nèi)ROS升高損傷DNA,激活線粒體凋亡途徑而誘導(dǎo)人卵巢癌SKOV3、A2780細(xì)胞凋亡。
[Abstract]:Objective to investigate the effect of (thioridazine), a dopamine receptor blocker, on the proliferation and apoptosis of ovarian cancer cell line SKOV3,A2780 and its possible mechanism. Methods SKOV3,A2780 cells were treated with different concentrations of thiridazide (0 0101010 ~ 1520 渭 mol/L). CCK8 assay was used to detect cell proliferation, flow cytometry and DAPI staining were used to detect cell apoptosis, and DCFH-DA staining was used to detect the level of ROS. The damage of nuclear DNA was observed by comet assay. Mitochondrial membrane potential was detected by JC-1 staining., Western blot was used to detect the expression of P53 Bax-Bcl-2 and cytochrome active Caspase-3 protein. Results the proliferation of human ovarian cancer cell line SKOV3,A2780 was inhibited by thiridamine in a dose-dependent manner (P0.05). When the concentration was 15 渭 mol/L, the proliferation inhibition effect was obvious. Flow cytometry analysis showed that the apoptotic rate of the treatment group (15 渭 mol/L tiridamine for 24 h) was significantly higher than that of the control group (P0.05); DAPI staining results: the treatment group showed obvious nuclear pyknosis, fragmentation and apoptotic bodies; The level of ROS in DCFH-DA staining group was higher than that in control group (P0.05); Comet assay showed obvious DNA damage in treatment group; JC-1 staining showed that mitochondrial membrane potential in treatment group was lower than that in control group (P0.05). Western blot assay showed that the expression of cytochrome C active Caspase-3 in cytochrome C was up-regulated and the expression of cytochrome C in mitochondria of Bcl-2, was down-regulated in the treatment group. Conclusion tiridazide may induce apoptosis of human ovarian cancer SKOV3,A2780 cells by inducing increased DNA, damage and mitochondrial apoptosis in human ovarian cancer SKOV3,A2780 cells.
【作者單位】： 重慶醫(yī)科大學(xué)附屬第二醫(yī)院婦產(chǎn)科;重慶醫(yī)科大學(xué)附屬第二醫(yī)院康復(fù)科;
【基金】：國(guó)家自然科學(xué)基金面上項(xiàng)目(81172492) 重慶市科委重點(diǎn)項(xiàng)目(CSTC2012JJB10030)~~
【分類(lèi)號(hào)】：R737.31

【共引文獻(xiàn)】

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7 王s，

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