【摘要】：目的:探討甲基蓮心堿(Nef)對(duì)人結(jié)腸癌細(xì)胞奧沙利鉑(OXA)耐藥的逆轉(zhuǎn)作用及機(jī)制。方法:采用OXA濃度逐步遞增法(2、4、8、12、24、48μmol/L)孵育人結(jié)腸癌HCT116細(xì)胞誘導(dǎo)構(gòu)建OXA耐藥株HCT116/OXA;檢測(cè)Nef對(duì)HCT116/OXA細(xì)胞的細(xì)胞毒性,確定Nef的最適作用濃度和時(shí)間;分析并比較OXA(IC_(50)濃度)單獨(dú)處理、Nef(最適作用濃度)單獨(dú)處理、OXA(IC_(50)濃度)聯(lián)合Nef(最適作用濃度)處理后,HCT116/OXA細(xì)胞的增殖,凋亡情況及凋亡相關(guān)蛋白(Bcl-2,Bax,PARP,p-PARP)的表達(dá)情況。結(jié)果:與親本HCT116細(xì)胞比較,HCT116/OXA細(xì)胞較對(duì)OXA的耐藥性明顯增高(IC_(50):21.00μmol/Lvs.112.00μmol/L,P0.05),耐藥指數(shù)為5.33。Nef能明顯抑制HCT116/OXA的增殖有作用(P0.05),并呈濃度依賴(lài)性,其最適作用濃度、時(shí)間分別為5μmol/L、24h(細(xì)胞存活率為90%)。與OXA單獨(dú)處理比較,HCT116/OXA細(xì)胞對(duì)OXA聯(lián)合Nef處理的耐受性明顯降低(IC_(50):112.00μmol/Lvs.45.47μmol/L,P0.05),逆轉(zhuǎn)倍數(shù)為2.46;Nef單獨(dú)作用對(duì)HCT116/OXA細(xì)胞的凋亡影響不明顯(P0.05),但其與OXA聯(lián)合作用對(duì)HCT116/OXA細(xì)胞凋亡誘導(dǎo)作用明顯強(qiáng)于OXA單獨(dú)作用(P0.05);與OXA或Nef單獨(dú)作用比較,OXA聯(lián)合Nef作用后,HCT116/OXA細(xì)胞抗凋亡蛋白Bcl-2表達(dá)明顯下降,Bax、p-PARP等凋亡蛋白表達(dá)明顯上升(均P0.05)。結(jié)論:Nef可逆轉(zhuǎn)HCT116/OXA對(duì)OXA的耐藥,機(jī)制可能與其調(diào)節(jié)Bcl-2/Bax表達(dá)水平,從而與OXA產(chǎn)生協(xié)同作用有關(guān)。
[Abstract]:Aim: to investigate the reversal effect of (Nef) on oxaliplatin (OXA) resistance in human colon cancer cells and its mechanism. Methods: human colon cancer HCT116 cells were incubated with the method of increasing the concentration of OXA (2? 4? 48 渭 mol/L). The OXA resistant cell line HCT116/OXA; was used to detect The proliferation of HCT116/OXA cells treated with OXA (IC_ (50) concentration alone), OXA (IC_ (50) concentration alone and Nef (optimal concentration) was analyzed and compared. Apoptosis and expression of apoptosis-related protein (Bcl-2,Bax,PARP,p-PARP). Results: compared with parental HCT116 cells, the resistance of HCT116/OXA cells to OXA was significantly higher than that of HCT116/OXA cells (IC_ (50): 21.00 渭 mol/Lvs.112.00 渭 mol/L,P0.05). The drug resistance index (5.33.Nef) could significantly inhibit the proliferation of HCT116/OXA (P0.05) in a concentration-dependent manner, and the optimal concentration was 5 渭 mol/L,24h (cell survival rate was 90%). Compared with OXA alone, the tolerance of HCT116/OXA cells to OXA combined with Nef was significantly decreased (IC_ (50): 112.00 渭 mol/Lvs.45.47 渭 mol/L,P0.05), and the reversal multiple was 2.46; The effect of Nef alone on the apoptosis of HCT116/OXA cells was not significant (P0.05), but the combined effect of Nef and OXA on the apoptosis of HCT116/OXA cells was significantly stronger than that of OXA alone (P0.05). Compared with OXA or Nef alone, OXA combined with Nef significantly decreased the expression of anti-apoptotic protein Bcl-2 and increased the expression of Bax,p-PARP and other apoptotic proteins in HCT116/OXA cells (P0.05). Conclusion: Nef can reverse the drug resistance of HCT116/OXA to OXA, and the mechanism may be related to the regulation of Bcl-2/Bax expression and the synergistic effect of OXA.
【作者單位】： 中南大學(xué)湘雅醫(yī)院醫(yī)學(xué)科學(xué)研究中心;中南大學(xué)湘雅醫(yī)院腫瘤科;湖南省分子放射腫瘤學(xué)重點(diǎn)實(shí)驗(yàn)室;
【基金】：國(guó)家自然科學(xué)基金資助項(xiàng)目(30770970;81172471;81070362;81372629) 湖南省自然科學(xué)基金重點(diǎn)資助項(xiàng)目(11JJ2049)
【分類(lèi)號(hào)】：R735.35

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