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CDK抑制劑NSC649890聯(lián)合順鉑對人骨肉瘤細(xì)胞U2-OS的抑制作用

發(fā)布時(shí)間:2018-02-03 16:15

  本文關(guān)鍵詞: 人骨肉瘤U-OS細(xì)胞 CDK抑制劑 順鉑 細(xì)胞增殖 細(xì)胞凋亡 出處:《中國矯形外科雜志》2017年01期  論文類型:期刊論文


【摘要】:[目的]探討CDK抑制劑NSC 649890聯(lián)合順鉑對人骨肉瘤U2-OS細(xì)胞抑制作用及可能的機(jī)制。[方法]MTT法檢測分別采用50、100、200、400、800 nmol/L的NSC 649890 2、4、6、8、10μg/ml順鉑、50 nmol的NSC649890聯(lián)合2μg/ml順鉑、300nmol的NSC 649890聯(lián)合6μg/ml順鉑培養(yǎng)48 h后細(xì)胞增殖情況,金氏q值評價(jià)聯(lián)合用藥效應(yīng);流式細(xì)胞儀、Western blotting檢測分別采用300 nmol/L的NSC 649890、6μg/ml順鉑及二者聯(lián)合培養(yǎng)48 h后細(xì)胞凋亡及凋亡通路相關(guān)蛋白表達(dá)情況,以上實(shí)驗(yàn)均以單純U2-OS細(xì)胞作為對照組。[結(jié)果]U2-OS細(xì)胞經(jīng)不同濃度順鉑、NSC 649890單獨(dú)處理48 h后,細(xì)胞抑制率隨兩種藥物濃度增加而顯著升高,比較差異均有統(tǒng)計(jì)學(xué)意義(P0.05)。在聯(lián)合用藥組中,順鉑與NSC 649890聯(lián)合濃度(2μg/ml+50 nmol/L)組兩藥為協(xié)同作用,(6μg/ml+300nmol/L)組兩藥為相加作用。流式細(xì)胞儀檢測顯示,順鉑組、NSC 649890組及聯(lián)合組細(xì)胞凋亡率顯著高于對照組(P0.05)。Western blotting檢測結(jié)果顯示,與對照組相比,順鉑和NSC 649890單獨(dú)作用后均可下調(diào)Bcl-2蛋白、procaspase-3蛋白的表達(dá)水平及上調(diào)Bax蛋白的表達(dá)水平,差異均有統(tǒng)計(jì)學(xué)意義(P0.05),而兩者聯(lián)合作用時(shí)效果更加顯著(P0.05)。[結(jié)論]NSC 649890能增強(qiáng)順鉑對人骨肉瘤U2-OS細(xì)胞的抑制作用。
[Abstract]:[Objective] to investigate the inhibitory effect of CDK inhibitor NSC 649890 combined with cisplatin on human osteosarcoma U2-OS cells and its possible mechanism. [Methods] MTT method was used to detect cisplatin 10 渭 g / ml of 50,100,200,400,800 nmol/L NSC (649890 2G / ml). The proliferation of 50 nmol NSC649890 combined with 2 渭 g / ml Cisplatin 300nmol NSC649890 and 6 渭 g / ml Cisplatin for 48 h was observed. Kim's Q value was used to evaluate the effect of combined medication. Western blotting was used to detect NSC 649890 of 300 nmol/L by flow cytometry. 6 渭 g / ml cisplatin and co-cultured with cisplatin and both for 48 h, apoptosis and apoptosis-pathway related protein expression, U2-OS cells were used as control group. [Results: the inhibition rate of U2-OS cells increased significantly with the increase of the concentration of two drugs after 48 hours of treatment with different concentrations of cisplatin or NSC 649890 alone. The difference was statistically significant in the combination group. The synergistic effect of cisplatin and NSC 649890 was observed in 2 渭 g / ml 50 nmol / L group. 6 渭 g / ml 300nmol / L) group was additive. Flow cytometry showed that the cisplatin group was treated with Cisplatin. The rate of apoptosis in NSC 649890 group and combined group was significantly higher than that in control group (P 0.05). Western blotting assay showed that the apoptosis rate was significantly higher than that in control group. Both cisplatin and NSC 649890 could down-regulate the expression of Bcl-2 protein procaspase-3 and up-regulate the expression of Bax protein. The difference was statistically significant (P 0.05), and the effect of combined action was more significant than that of P0.05 (P 0.05). [Conclusion NSC 649890 can enhance the inhibitory effect of cisplatin on human osteosarcoma U2-OS cells.
【作者單位】: 南昌大學(xué)第一附屬醫(yī)院骨科;
【基金】:江西省衛(wèi)生廳科技計(jì)劃資助項(xiàng)目(編號(hào):20091059),江西省衛(wèi)生廳中醫(yī)藥科研課題(編號(hào):2012A136) 江西省自然基金資助項(xiàng)目(編號(hào):2010JX02603;20132BAB205081)
【分類號(hào)】:R738.1
【正文快照】: 骨肉瘤是一種主要發(fā)病人群為青少年的原發(fā)性惡性腫瘤,其強(qiáng)侵襲性常導(dǎo)致患者早期即出現(xiàn)腫瘤細(xì)胞遠(yuǎn)處轉(zhuǎn)移。目前應(yīng)對骨肉瘤的臨床治療主要以化療-手術(shù)-化療為主[1-2]。順鉑是骨肉瘤化療的常見藥物之一,但臨床證實(shí)骨肉瘤細(xì)胞對順鉑易產(chǎn)生耐藥性[3-4]。小分子細(xì)胞周期素依賴性蛋白,

本文編號(hào):1487813

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