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聚乙烯醇促进了PK - 8胰腺导管腺癌细胞系的生长、迁移、侵袭以及球体大小。

Polyvinyl alcohol increased growth, migration, invasion, and sphere size in the PK-8 pancreatic ductal adenocarcinoma cell line.

作者信息

Gomi Fujiya, Sasaki Norihiko, Shichi Yuuki, Minami Fuuka, Shinji Seiichi, Toyoda Masashi, Ishiwata Toshiyuki

机构信息

Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan.

Research Team for Geriatric Medicine (Vascular Medicine), Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan.

出版信息

Heliyon. 2021 Feb 4;7(2):e06182. doi: 10.1016/j.heliyon.2021.e06182. eCollection 2021 Feb.

Abstract

Polyvinyl alcohol (PVA) is a water-soluble synthetic polymer used in eye drops, embolization particles, and artificial cartilage. It has also been shown to cause expansion of functional multipotent self-renewing hematopoietic stem cells under serum-free conditions. In this study, we examined the effects of PVA on human pancreatic ductal adenocarcinoma (PDAC) cell lines using 2-dimensional (2D) and 3D-cultures with serum-free medium. In the 2D-culture, PVA-treatment induced an aggregated colony-like appearance in PDAC cells. It increased the growth of PK-8 cells in a dose-dependent manner as well as significantly increasing migration and invasion abilities. qRT-PCR showed an increase in α2 integrin and a decrease in matrix metalloprotease levels in PVA-treated PK-8 cells. Through qRT-PCR analysis, β1 integrin expression at the mRNA level was found to be decreased; however, it was unaltered at the protein level when assessed using FACS analysis. PVA further induced mesenchymal to epithelial transition-like alterations, including increased E-cadherin and decreased Vimentin and N-cadherin expression. Four cancer stem cell (CSC) markers were higher in PVA-treated PK-8 cells compared to controls. In 3D-culture, PVA-treated PK-8 cells showed a rod-like appearance with larger sphere size and higher growth ability. qRT-PCR showed that CSC markers did not increase and 2 of 4 drug transporters had decreased in PVA-treated PK-8 cells. These findings suggest that PVA increases the growth, migration, invasion, and sphere size of PK-8 cells, but does not increase the proportion of pancreatic CSCs under 3D-culture conditions with serum-free medium.

摘要

聚乙烯醇(PVA)是一种水溶性合成聚合物,用于眼药水、栓塞颗粒和人工软骨。研究还表明,在无血清条件下,它能促使功能性多能自我更新造血干细胞扩增。在本研究中,我们使用无血清培养基的二维(2D)和三维(3D)培养方法,检测了PVA对人胰腺导管腺癌(PDAC)细胞系的影响。在2D培养中,PVA处理使PDAC细胞呈现聚集的集落样外观。它以剂量依赖的方式促进PK - 8细胞生长,同时显著提高其迁移和侵袭能力。qRT - PCR显示,PVA处理的PK - 8细胞中α2整合素增加,基质金属蛋白酶水平降低。通过qRT - PCR分析发现,β1整合素在mRNA水平表达降低;然而,使用流式细胞术分析时,其蛋白水平未发生改变。PVA还诱导了间充质向上皮样转变,包括E - 钙黏蛋白增加,波形蛋白和N - 钙黏蛋白表达降低。与对照组相比,PVA处理的PK - 8细胞中四种癌症干细胞(CSC)标志物水平更高。在3D培养中,PVA处理的PK - 8细胞呈棒状外观,球体更大,生长能力更强。qRT - PCR显示,PVA处理的PK - 8细胞中CSC标志物没有增加,4种药物转运蛋白中有2种减少。这些发现表明,在无血清培养基的3D培养条件下,PVA可增加PK - 8细胞的生长、迁移、侵袭能力和球体大小,但不会增加胰腺CSC的比例。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46d7/7868635/b26bd64889a5/gr1.jpg

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