Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway
Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway
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DOI：
10.1038/s41598-020-58667-3
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发表时间：
2020-01
影响因子：
4.6
通讯作者：
N. Yoshikawa;Wenting Liu;Kae Nakamura;Kosuke Yoshida;Y. Ikeda;Hiromasa Tanaka;M. Mizuno;S. Toyokuni;M. Hori;F. Kikkawa;H. Kajiyama
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文献类型：
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作者：
N. Yoshikawa;Wenting Liu;Kae Nakamura;Kosuke Yoshida;Y. Ikeda;Hiromasa Tanaka;M. Mizuno;S. Toyokuni;M. Hori;F. Kikkawa;H. Kajiyama
非热大气压等离子体的生物学功能已被广泛接受的几种类型的癌症。我们以前开发了血浆激活培养基（PAM）的临床应用，并证明，PAM表现出转移抑制卵巢癌通过减少MMP-9分泌的影响。然而，PAM对子宫内膜癌的抗肿瘤作用仍然未知。本研究旨在探讨PAM对子宫内膜癌细胞生长的抑制作用。我们的结果表明，PAM在一定比例下降低AMEC和HEC 50细胞的活力，并且PAM处理以浓度依赖性方式有效地增加自噬性细胞死亡。此外，我们评估了PAM活性的分子机制，发现PAM使mTOR通路失活。此外，我们的结果表明，自噬抑制剂MHY 1485部分抑制PAM处理诱导的自噬细胞死亡。这些发现表明，PAM降低子宫内膜癌细胞的活力沿着mTOR途径的改变，这对癌细胞活力至关重要。总的来说，我们的数据表明，PAM抑制细胞活力，同时诱导子宫内膜癌细胞的自噬性细胞死亡，代表了一种潜在的新的治疗子宫内膜癌。
The biological function of non-thermal atmospheric pressure plasma has been widely accepted in several types of cancer. We previously developed plasma-activated medium (PAM) for clinical use, and demonstrated that PAM exhibits a metastasis-inhibitory effect on ovarian cancer through reduced MMP-9 secretion. However, the anti-tumor effects of PAM on endometrial cancer remain unknown. In this study, we investigated the inhibitory effect of PAM on endometrial cancer cell viabilityin vitro. Our results demonstrated that AMEC and HEC50 cell viabilities were reduced by PAM at a certain PAM ratio, and PAM treatment effectively increased autophagic cell death in a concentration dependent manner. In addition, we evaluated the molecular mechanism of PAM activity and found that the mTOR pathway was inactivated by PAM. Moreover, our results demonstrated that the autophagy inhibitor MHY1485 partially inhibited the autophagic cell death induced by PAM treatment. These findings indicate that PAM decreases the viability of endometrial cancer cells along with alteration of the mTOR pathway, which is critical for cancer cell viability. Collectively, our data suggest that PAM inhibits cell viability while inducing autophagic cell death in endometrial cancer cells, representing a potential novel treatment for endometrial cancer.