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Neuroendocrine differentiation is involved in chemoresistance induced by EGF in prostate cancer cells.

机译:神经内分泌分化与前列腺癌细胞中EGF诱导的化学耐药有关。

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AIMS: Neuroendocrine (NE) cells were thought to be post-mitotic and non-proliferative. But it was recently reported that NE cells express, and induce surrounding cells to express potent antiapoptotic proteins. We hypothesize that neuroendocrine differentiation (NED), a common phenomenon in prostate cancer, is related to chemoresistance in prostate cancer. MAIN METHODS: Androgen-independent human prostate cancer DU145 and PC-3 cells were exposed to epidermal growth factor (EGF). MTT assays evaluated changes in chemoresistance after EGF treatment, and flow cytometry examined EGF-induced cell cycle changes in DU145 cells. Western blotting, real-time RT-PCR and transmission electron microscopy were utilized to confirm NED. KEY FINDINGS: After stimulation with EGF, DU145 and PC-3 cells exhibited stronger resistance to cisplatin. Flow cytometry showed that EGF stimulation substantially decreased the proportion of DU145 cells in G(1) phase. EGF treatment increased the expression of neuron-specific enolase, a marker of NED induction. SIGNIFICANCE: NED in prostate cancer is involved in the chemoresistance induced by EGF. EGF and/or the EGF receptor may be potential targets for medical intervention in chemo-resistant prostate cancer.
机译:目的:神经内分泌(NE)细胞被认为是有丝分裂后和非增殖性的。但是最近有报道说,NE细胞表达并诱导周围细胞表达有效的抗凋亡蛋白。我们假设神经内分泌分化(NED),在前列腺癌中很常见,与前列腺癌的化学抗性有关。主要方法:非雄激素依赖性人类前列腺癌DU145和PC-3细胞暴露于表皮生长因子(EGF)。 MTT分析评估了EGF处理后化学抗性的变化,流式细胞仪检查了DU145细胞中EGF诱导的细胞周期变化。 Western blotting,实时RT-PCR和透射电镜证实NED。主要发现:用EGF刺激后,DU145和PC-3细胞对顺铂表现出更强的抵抗力。流式细胞仪显示,EGF刺激大大减少了DU145细胞在G(1)期的比例。 EGF处理可增加神经元特异性烯醇化酶(NED诱导的标志物)的表达。意义:前列腺癌中的NED与EGF诱导的化学耐药有关。 EGF和/或EGF受体可能是对化学耐药性前列腺癌进行医学干预的潜在靶标。

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