Spermidine-induced growth inhibition and apoptosis via autophagic activation in cervical cancer
Spermidine-induced growth inhibition and apoptosis via autophagic activation in cervical cancer
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DOI：
10.3892/or.2018.6377
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发表时间：
2018-06-01
期刊：
影响因子：
4.2
通讯作者：
Wang, Xu
中科院分区：
文献类型：
--
作者：
Chen, Yu;Zhuang, Haifeng;Wang, Xu
宫颈癌是女性生殖道最常见的恶性肿瘤，对预防性疫苗的不良反应和大剂量化疗药物的毒性限制了其临床应用。亚精胺是一种天然多胺，存在于所有真核生物中，在多种模式系统中显示出促进寿命的功能，可能是一种有前景的癌症治疗药物。然而，亚精胺在宫颈癌中的潜在疗效尚未完全阐明，其潜在的分子机制尚不清楚。在本研究中，我们旨在评估亚精胺对宫颈癌细胞系HeLa细胞增殖和凋亡的影响。首先，CCK-8和流式细胞术分析显示，亚精胺通过在S期阻断细胞周期，以剂量依赖的方式降低HeLa细胞的增殖。其次，结合Annexin V-FITC/ pi染色的流式细胞术显示亚精胺促进HeLa细胞凋亡，western blot分析显示亚精胺激活自噬。最后，亚精胺激活的自噬介导了亚精胺对HeLa细胞增殖的抑制和亚精胺诱导的细胞凋亡。总之，这些结果揭示了亚精胺通过激活自噬来抑制细胞增殖和诱导HeLa细胞凋亡的新功能，这可能对亚精胺在宫颈癌治疗中的应用具有重要意义。
Cervical cancer is the most common malignancy of the female reproductive tract, and the poor response to prophylactic vaccines and the toxicity of high-dose chemotherapeutic drugs have limited their clinical application. Spermidine, a natural polyamine detected in all eukaryotic organisms, exhibits functions that promote longevity in multiple model systems and may constitute a promising agent for cancer treatment. However, the potential effectiveness of spermidine in cervical cancer has not yet been fully elucidated, and the underlying molecular mechanisms remain unclear. In the present study, we aimed to assess the effects of spermidine on proliferation and apoptosis of HeLa cells (a cervical cancer cell line). Firstly, CCK-8 and flow cytometric assays revealed that spermidine reduced the proliferation of HeLa cells in a dose-dependent fashion by arresting the cell cycle at the S phase. Secondly, flow cytometry incorporating Annexin V-FITC/PI-staining revealed that spermidine promoted the apoptosis of HeLa cells, and western blot analysis revealed that spermidine activated autophagy. Finally, spermidine-activated autophagy mediated the inhibition of cell proliferation by spermidine and spermidine-induced apoptosis in HeLa cells. Collectively, these results revealed a novel function for spermidine in inhibiting cellular proliferation and inducing apoptosis of HeLa cells by activating autophagy, which may have important implications for the use of spermidine in cervical cancer therapy.