Zeng Tianjiao, Lu Chengyu, Wang Man, Chen Huajian, Yoshitomi Toru, Kawazoe Naoki, Yang Yingnan, Chen Guoping
Research Center for Macromolecules and Biomaterials, National Institute for Materials Science, Ibaraki 305-0044, Japan.
Graduate School of Science and Technology, University of Tsukuba, Ibaraki 305-8577, Japan.
J Mater Chem B. 2025 Feb 5;13(6):2180-2191. doi: 10.1039/d4tb02334j.
The colon possesses a unique physiological environment among human organs, where there is a highly viscous body fluid layer called the mucus layer above colonic epithelial cells. Dysfunction of the mucus layer not only contributes to the occurrence of colorectal cancer (CRC) but also plays an important role in the development of chemoresistance in CRC. Although viscosity is an essential property of the mucus layer, it remains elusive how viscosity affects chemoresistance in colon cancer cells. In this study, the influence of viscosity on their chemoresistance was elucidated by culturing colon cancer cells in media of different viscosities supplemented with doxorubicin (DOX). The viscosity range was adjusted from 99.4 mPa s to 776.6 mPa s by adding polyethylene glycol of different molecular weights in culture medium. Cell viability in the high viscosity medium was higher than that in the low viscosity medium. Expression of chemoresistance-related genes such as ABCC2 and ABCG2 increased when cells were cultured in the high viscosity medium. Furthermore, cell migration increased while proliferation decreased when cells were cultured in the high viscosity medium. The colon cancer cells cultured in the high viscosity medium exhibited high expression of p21 mRNA. The results suggested that viscosity could affect the resistance of colon cancer cells to DOX by regulating the expression of chemoresistance-related and proliferation-related genes.
在人体器官中，结肠拥有独特的生理环境，结肠上皮细胞上方存在一层名为黏液层的高黏性体液层。黏液层功能失调不仅会导致结直肠癌（CRC）的发生，还在CRC化疗耐药的发展中起重要作用。尽管黏度是黏液层的一项基本特性，但黏度如何影响结肠癌细胞的化疗耐药性仍不清楚。在本研究中，通过在添加阿霉素（DOX）的不同黏度培养基中培养结肠癌细胞，阐明了黏度对其化疗耐药性的影响。通过在培养基中添加不同分子量的聚乙二醇，将黏度范围从99.4毫帕秒调整到776.6毫帕秒。高黏度培养基中的细胞活力高于低黏度培养基中的细胞活力。当细胞在高黏度培养基中培养时，ABCC2和ABCG2等化疗耐药相关基因的表达增加。此外，当细胞在高黏度培养基中培养时，细胞迁移增加而增殖减少。在高黏度培养基中培养的结肠癌细胞表现出p21 mRNA的高表达。结果表明，黏度可通过调节化疗耐药相关基因和增殖相关基因的表达来影响结肠癌细胞对DOX的耐药性。
