【摘要】：目的 研究新型小分子化合物CC1007與順鉑聯(lián)合使用對(duì)宮頸癌細(xì)胞化療效果的影響及其可能的分子機(jī)制。 方法 1.四甲基偶氮唑藍(lán)(MTT)比色法檢測(cè)對(duì)照組、CC1007單藥組、順鉑單藥組及CC1007+順鉑聯(lián)合用藥組作用48小時(shí)對(duì)體外培養(yǎng)的人宮頸癌細(xì)胞株HeLa、Caski增殖的抑制效應(yīng),計(jì)算藥物的半抑制率(IC50),并繪制濃度-抑制率曲線。實(shí)驗(yàn)重復(fù)3次。 2.Western blot檢測(cè)對(duì)照組、CC1007單藥組、順鉑單藥組及CC1007+順鉑聯(lián)合用藥組作用24小時(shí)凋亡相關(guān)蛋白Nur77的表達(dá)。實(shí)驗(yàn)重復(fù)3次。 3.對(duì)實(shí)驗(yàn)數(shù)據(jù)進(jìn)行統(tǒng)計(jì)學(xué)分析。 結(jié)果 1.MTT實(shí)驗(yàn)結(jié)果顯示CC1007及順鉑均對(duì)宮頸癌細(xì)胞HeLa、 Caski有抑制作用,且呈濃度依賴性,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。當(dāng)兩種藥物聯(lián)合作用時(shí),抑制作用更加明顯。在HeLa細(xì)胞中,順鉑的IC50由單藥應(yīng)用時(shí)的1.13μg/L降為聯(lián)合應(yīng)用時(shí)的0.520μg/L；在Caski細(xì)胞中,順鉑的IC50由單藥應(yīng)用時(shí)的1.55μg/L降為聯(lián)合應(yīng)用時(shí)的0.507μg/L,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。兩者聯(lián)合應(yīng)用時(shí)可發(fā)揮協(xié)同效應(yīng)。 2. Western blot實(shí)驗(yàn)結(jié)果顯示在HeLa細(xì)胞中,順鉑單藥組及CC1007+順鉑聯(lián)合用藥組Nur77表達(dá)較對(duì)照組均升高,差異有統(tǒng)計(jì)學(xué)意義(P0.05)；順鉑單藥組及CC1007+順鉑聯(lián)合用藥組之間Nur77的表達(dá)差異有統(tǒng)計(jì)學(xué)意義(P0.05)。在Caski細(xì)胞中,CC1007單藥組、順鉑單藥組及CC1007+順鉑聯(lián)合用藥組Nur77的表達(dá)較對(duì)照組均升高,差異有統(tǒng)計(jì)學(xué)意義(P0.05)；順鉑單藥組及CC1007+順鉑聯(lián)合用藥組之間Nur77的表達(dá)差異有統(tǒng)計(jì)學(xué)意義(P0.05)。 結(jié)論 1.CC1007與順鉑均對(duì)人宮頸癌細(xì)胞株有抑制作用,且呈濃度依賴性,CC1007可增加人宮頸癌細(xì)胞株對(duì)順鉑的敏感性,兩者聯(lián)合作用可發(fā)揮協(xié)同效應(yīng)。 2.在人宮頸癌細(xì)胞株HeLa、Caski中,順鉑可上調(diào)Nur77的表達(dá),與CC1007聯(lián)合應(yīng)用,Nur77表達(dá)明顯升高,這可能是CC1007與順鉑發(fā)揮協(xié)同效應(yīng)的分子機(jī)制。
[Abstract]:Objective to study the effect of CC1007 combined with cisplatin on the chemotherapeutic effect of cervical cancer cells and its possible molecular mechanism. Method 1. The inhibitory effects of (MTT) colorimetric assay on the proliferation of human cervical cancer cell line HeLa,Caski in vitro were detected by (MTT) colorimetric assay in the control group, single CC1007 group, cisplatin group and CC1007 cisplatin group for 48 hours. The semi-inhibition rate (IC50) of the drug was calculated and the concentration-inhibition rate curve was drawn. The experiment was repeated three times. 2.Western blot was used to detect the expression of apoptosis-related protein (Nur77) in control group, CC1007 group, cisplatin group and CC1007 cisplatin group. The experiment was repeated three times. 3. The experimental data were analyzed statistically. Results 1.MTT results showed that both CC1007 and cisplatin could inhibit HeLa, Caski of cervical cancer cells in a dose-dependent manner, and the difference was statistically significant (P0.05). When the two drugs combined, the inhibitory effect was more obvious. In HeLa cells, the IC50 of cisplatin decreased from 1.13 渭 g / L to 0.520 渭 g / L in combination. In Caski cells, the IC50 of cisplatin decreased from 1.55 渭 g / L to 0.507 渭 g / L (P0.05). The synergistic effect can be brought into play when the two are applied in combination. 2. Western blot results showed that in HeLa cells, the Nur77 expression in cisplatin monotherapy group and CC1007 cisplatin combination group were higher than that in control group (P0.05). There was significant difference in the expression of Nur77 between cisplatin monotherapy group and CC1007 cisplatin combination group (P0.05). In Caski cells, the expression of Nur77 in CC1007 monotherapy group, cisplatin monotherapy group and CC1007 cisplatin combination group were significantly higher than that in control group (P0.05). There was significant difference in the expression of Nur77 between cisplatin monotherapy group and CC1007 cisplatin combination group (P0.05). Conclusion both 1.CC1007 and cisplatin can inhibit human cervical cancer cell line in a concentration-dependent manner. CC1007 can increase the sensitivity of human cervical cancer cell line to cisplatin. 2. In human cervical cancer cell line HeLa,Caski, cisplatin can up-regulate the expression of Nur77, and when combined with CC1007, the expression of Nur77 is significantly increased, which may be the molecular mechanism of synergistic effect of CC1007 and cisplatin.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R737.33

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