發(fā)布時(shí)間：2018-06-08 11:10

  本文選題：全反式維甲酸 + 多西紫杉醇��； 參考：《昆明醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的： 探討ATRA聯(lián)合DOC對(duì)雄激素非依賴性前列腺癌細(xì)胞株P(guān)C-3的作用。 方法： 將體外培養(yǎng)的前列腺癌PC-3細(xì)胞分為對(duì)照組(僅加培養(yǎng)基)、ATRA組(10-5mol/L ATRA處理)、DOC組(10-6mol/L DOC處理)及聯(lián)合組(10-5mol/L ATRA+10-6mol/L DOC處理),作用24h。利用比色法(MTS法)測(cè)定細(xì)胞增殖抑制情況；普通光學(xué)顯微鏡觀察細(xì)胞形態(tài)學(xué)的變化；流式細(xì)胞儀測(cè)定細(xì)胞周期時(shí)相變化及檢測(cè)細(xì)胞凋亡；流式細(xì)胞儀檢測(cè)CD133+CD44+細(xì)胞比例。 結(jié)果： ATRA和DOC均可抑制前列腺癌PC-3細(xì)胞增殖,10-5、10-6、10-7mol/L ATRA作用24h后對(duì)PC-3細(xì)胞抑制率分別為37.7%、32.9%、28.2%,10-6、10-7、10-8mol/L DOC作用24h后對(duì)PC-3細(xì)胞抑制率分別為43.7%、36.2%、32.8%,呈劑量依賴效應(yīng),聯(lián)合用藥組作用24h后的細(xì)胞抑制率為59.3%,明顯高于單獨(dú)用藥組(P0.05),提示聯(lián)合用藥后對(duì)前列腺癌PC-3細(xì)胞的抑制作用高于單獨(dú)用藥；普通光學(xué)顯微鏡觀察到ATRA和DOC均導(dǎo)致細(xì)胞皺縮、核質(zhì)濃縮、核碎裂等凋亡形態(tài)學(xué)改變,聯(lián)合用藥組表現(xiàn)更明顯；流式細(xì)胞儀檢測(cè)顯示10-5mol/L ATRA作用24h后PC-3的細(xì)胞凋亡率為10.05%,10-6mol/L DOC作用24h后PC-3的細(xì)胞凋亡率為12.51%,聯(lián)合用藥組作用24h后PC-3的細(xì)胞凋亡率為19.38%,聯(lián)合用藥組顯著高于單獨(dú)用藥組(P0.05),提示聯(lián)合用藥對(duì)前列腺癌PC-3細(xì)胞的促凋亡作用高于單獨(dú)用藥；ATRA所致的細(xì)胞周期阻滯以Go/G1期為主,DOC所致的細(xì)胞周期阻滯以G2/M期為主,聯(lián)合用藥后G2/M期比例有所下降,同時(shí)Go/G1期比例明顯增加,提示聯(lián)合用藥后細(xì)胞周期比例變化差異有顯著性(P0.05)；流式細(xì)胞儀檢測(cè)顯示ATRA處理后PC-3細(xì)胞中CD133+CD44+細(xì)胞比例為0.2%、較陰性組0.6%下降,DOC處理后PC-3細(xì)胞中CD133+CD44+細(xì)胞比例為3.3%、較陰性組上升,與ATRA組相比差異顯著(P0.05),聯(lián)合用藥組處理后CD133+CD44+細(xì)胞比例為0.2%,與ATRA組相比無(wú)顯著差異(P0.05),提示ATRA可能具有促進(jìn)前列腺癌干細(xì)胞分化的作用。 結(jié)論： 1.DOC作用于前列腺癌PC-3細(xì)胞能導(dǎo)致細(xì)胞凋亡,但腫瘤干細(xì)胞比例卻明顯升高。 2.ATRA能夠降低前列腺癌PC-3的干細(xì)胞比例,提示ATRA可能具有分化前列腺癌干細(xì)胞的作用。 3.ATRA聯(lián)合DOC可協(xié)同抑制前列腺癌PC-3細(xì)胞的增殖,增強(qiáng)二者的促凋亡作用。
[Abstract]:Objective: to investigate the effect of ATRA combined with DOC on androgen independent prostate cancer cell line PC-3. Methods: PC-3 cells cultured in vitro were divided into control group (10-5 mol / L ATRA treated with 10-5 mol / L ATRA) and PC-3 cells treated with 10-6 mol / L DOC in ATRA group; The combined group treated with 10-5 mol / L ATRA 10-6 mol / L DOC for 24 h. Cell proliferation inhibition was measured by colorimetric assay (MTS), morphological changes were observed by ordinary optical microscope, phase changes and apoptosis were detected by flow cytometry (FCM). Results: both ATRA and DOC could inhibit the proliferation of PC-3 cells by flow cytometry. The inhibitory rates of ATRA and DOC on PC-3 cells were 37.7% and 32.7 mol / L ATRA for 24 h, respectively. The inhibitory rates of ATRA and DOC on PC-3 cells were 37.7% and 36.2mol / L, respectively, in a dose-dependent manner. The inhibition rate of PC-3 cells in combined treatment group was 59.3, which was significantly higher than that in single drug group, suggesting that the inhibitory effect of combined treatment on prostate cancer PC-3 cells was higher than that of PC-3 cells treated alone, and ATRA and DOC both caused cell shrinkage under general optical microscope. The morphological changes of apoptosis, such as nuclear cytoplasm concentration and nuclear fragmentation, were more obvious in the combination group. Flow cytometry analysis showed that the apoptosis rate of PC-3 was 10.05% after 24 h exposure to 10-5 mol / L ATRA, and 12.51% of PC-3 cells were treated with 10-6 mol / L DOC for 24 h. The apoptosis rate of PC-3 in combination group was 19.38 after 24 hours of treatment. The results showed that the apoptotic effect of combined therapy on prostate cancer PC-3 cells was higher than that induced by ATRA alone. The cell cycle arrest induced by G / G _ 1 phase and DOC was mainly G _ 2 / M phase. The proportion of G _ 2 / M phase decreased after combined medication, and the proportion of Go-R / G _ 1 phase increased significantly. The results of flow cytometry showed that the percentage of CD133 CD44 cells in PC-3 cells treated with ATRA was 0.2, and the percentage of CD133 CD44 cells in PC-3 cells treated with DOC decreased by 0.6% compared with negative group, which was higher than that in negative group. Compared with ATRA group, the ratio of CD133 CD44 cells was 0.25.There was no significant difference between ATRA group and ATRA group, suggesting that ATRA could promote the differentiation of prostate cancer stem cells. Conclusion: 1. DOC acts on prostate cancer PC-3. Cells can cause apoptosis. However, the percentage of tumor stem cells was significantly increased. 2. ATRA could reduce the percentage of PC-3 cells, suggesting that ATRA might have the function of differentiating prostate cancer stem cells. 3. ATRA combined with DOC could inhibit the proliferation of prostate cancer PC-3 cells. Enhance the apoptotic effect of both.
【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R737.25

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 歐揚(yáng);郭秀麗;;腫瘤干細(xì)胞及其耐藥機(jī)制[J];生理科學(xué)進(jìn)展;2007年02期

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本文編號(hào)：1995592