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首页> 外文期刊>International journal of oncology >Inhibition of hedgehog signaling depresses self-renewal of pancreatic cancer stem cells and reverses chemoresistance
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Inhibition of hedgehog signaling depresses self-renewal of pancreatic cancer stem cells and reverses chemoresistance

机译：刺猬信号的抑制抑制胰腺癌干细胞的自我更新并逆转化学耐药性

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Pancreatic cancer stem cells play a crucial role in tumorigenesis and chemoresistance. The Hedgehog signaling pathway is a key regulator in pancreatic tumorigenesis and drug resistance. To identify pancreatic cancer stem cells, tumorspheres derived from the PANC-1 pancreatic cancer cell line were cultured under a floating-culture system. PANC-1 tumorspheres possessed properties of self-renewal, differentiation, higher tumorigenesis and chemoresistance. It was observed that Hedgehog pathway is active in PANC-1 tumorspheres as shown by expression of hedgehog components Smo, Gil 1 and Gli 2, detected by quantitative RT-PCR and western blotting. After cyclopamine-mediated blockade of hedgehog, a decrease in proliferation of PANC-1 tumorspheres and G0/G1 transition were observed, as well as a decreased expression of Bmi-1 in PANC-1 tumorspheres. Cyclopamine reversed chemoresistance to gemcitabine, resulting in decreased expression of ABCG2 in PANC-1 tumorspheres. Taken together, our data indicate that PANC-1 tumorspheres have ‘stemness’ potential, and hedgehog signaling pathway plays an important role in the regulation of self-renewal and reversal of chemoresistance in cancer stem cells in pancreatic adenocarcinoma.
机译：胰腺癌干细胞在肿瘤发生和化学耐药中起关键作用。刺猬信号通路是胰腺肿瘤发生和耐药性的关键调节因子。为了鉴定胰腺癌干细胞，将来自PANC-1胰腺癌细胞系的肿瘤球在浮式培养系统中进行培养。 PANC-1肿瘤球具有自我更新，分化，更高的肿瘤发生和化学抗性的特性。如通过定量RT-PCR和蛋白质印迹检测到的刺猬组分Smo，Gil 1和Gli 2的表达所示，观察到刺猬途径在PANC-1肿瘤球中是活跃的。在环巴胺介导的刺猬阻断之后，观察到PANC-1肿瘤球的增殖减少和G0 / G1过渡，以及BNC-1在PANC-1肿瘤球中的表达下降。环巴胺逆转了对吉西他滨的化学耐药性，导致PANC-1肿瘤球中ABCG2的表达降低。综上所述，我们的数据表明，PANC-1肿瘤球具有“干性”潜能，而刺猬信号通路在胰腺癌癌干细胞的自我更新和化学抗性逆转的调节中起着重要作用。

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