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首页> 外文期刊>Tumour biology : >Inhibition of mdr1 by G-quadruplex oligonucleotides and reversal of paclitaxel resistance in human ovarian cancer cells
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Inhibition of mdr1 by G-quadruplex oligonucleotides and reversal of paclitaxel resistance in human ovarian cancer cells

机译：G-四链体寡核苷酸对mdr1的抑制作用和紫杉醇耐药性在人卵巢癌细胞中的逆转

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The expression of ATP-dependent efflux pump P-glycoprotein (P-gp) in cancer cells generally results in multidrug resistance (MDR) to chemotherapeutic drugs, which is the main cause of chemotherapy failure in cancer treatment. The intracellular drug levels could be increased by some MDR reversal agents that inhibited the drug efflux activity of P-gp. The synthesized DNA nucleic acids of G-quadruplex represent a novel and unique class of anti-cancer agents. While there was no report on the roles of DNA G-quadruplex oligonucleotides (GQ-ODNs) in the MDR reversal, the present study was performed to investigate the ability of synthesized GQ-ODNs to reverse P-gp-mediated MDR and its mechanism in paclitaxel (PTX)-resistant SKOV3 (SKOV3/PTX) cells and their sensitive cell lines SKOV3. The ability of GQ-ODNs to reverse drug resistance was evaluated by MTS assay. The results showed that GQ-ODNs can reverse PTX resistance effectively. The potential of GQ-ODNs as reversal agents was evaluated with the nude mice tumor xenograft model and showed that the co-administration of the GQ-ODNs and PTX had better effects and was also more evident than treatment with only PTX. The P-gp expression was assessed by the Western blot; it showed that SKOV3/PTX cells showed highly expressed P-gp protein, while their sensitive cells scarcely showed P-gp. The presence of GQ-ODNs efficiently decreased the P-gp expression, showing that GQ-ODNs could reverse P-gp-mediated MDR by decreasing the expression of P-gp. This study indicated that GQ-ODNs could effectively reverse P-gp-mediated PTX resistance by inhibiting the expression of P-gp and by the co-administration of GQ-ODNs and PTX that could increase the apoptosis of SKOV3/PTX cells. Thus, the synthesized GQ-ODNs may be a potential inhibitor to overcome drug resistance.
机译：ATP依赖性外排泵P糖蛋白（P-gp）在癌细胞中的表达通常会导致对化疗药物的多药耐药（MDR），这是癌症治疗中化疗失败的主要原因。某些MDR逆转剂可以抑制P-gp的药物外排活性，从而增加细胞内药物的水平。 G-四链体的合成DNA核酸代表了一类新颖独特的抗癌药。虽然尚无关于DNA G-四链体寡核苷酸（GQ-ODN）在MDR逆转中的作用的报道，但本研究旨在研究合成的GQ-ODN逆转P-gp介导的MDR的能力及其机制。耐紫杉醇（PTX）的SKOV3（SKOV3 / PTX）细胞及其敏感细胞系SKOV3。通过MTS分析评估了GQ-ODN逆转耐药性的能力。结果表明，GQ-ODNs可以有效逆转PTX抗性。用裸鼠肿瘤异种移植模型评估了GQ-ODNs作为逆转剂的潜力，并显示GQ-ODNs和PTX的共同给药具有更好的效果，并且比仅使用PTX的治疗更明显。通过Western印迹评估P-gp表达。这表明SKOV3 / PTX细胞显示高表达的P-gp蛋白，而其敏感细胞几乎不显示P-gp。 GQ-ODN的存在有效地降低了P-gp的表达，表明GQ-ODN可以通过降低P-gp的表达来逆转P-gp介导的MDR。这项研究表明，GQ-ODNs可以通过抑制P-gp的表达以及与GQ-ODNs和PTX的共同使用来有效逆转P-gp介导的PTX耐药性，这可以增加SKOV3 / PTX细胞的凋亡。因此，合成的GQ-ODNs可能是克服耐药性的潜在抑制剂。

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