title: Role of three-dimensional matrix stiffness in regulating the chemoresistance of hepatocellular carcinoma cells.
abstract: Hepatocellular carcinoma (HCC) was the most common primary liver cancer, and its resistance to anti-tumor drugs often caused the death of patients suffering with HCC. Matrix stiffness was reported to be closely related to tumor chemoresistance; however, the relationship between HCC drug resistance and three-dimensional (3D) matrix stiffness is still unclear at present. In this study, alginate gel (ALG) beads with controllable matrix stiffness were used to mimic tumor tissue rigidity, and the role of 3D matrix stiffness in regulating the chemoresistance of HCC cells was investigated by using these ALG beads. It was found that HCC cells in ALG beads with 105 kPa stiffness had highest resistance to paclitaxel, 5-FU, and cisplatin. Although the mechanism was still uncovered, ABC transporters and endoplasmic reticulum stress-related molecules were highly expressed in ALG bead-encapsulated HCC cells compared with two-dimensional-cultured cells, which suggested a very complex mechanism underlying HCC drug resistance in 3D culture conditions. In addition, to mimic the specific stiffness of HCC tumor tissue, or other tumor tissues in vivo, response surface methodology (RSM) was used to build up a prediction mathematical model so that ALG beads with desired matrix stiffness could be prepared by simply changing three factors: molecular weight, G content, and alginate concentration.
authors.affiliation: Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, People's Republic of China.|University of Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, People's Republic of China.
authors.forename: Hong-Guo
authors.initials: HG
authors.lastname: Xie
authors.affiliation: Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, People's Republic of China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, People's Republic of China.|University of Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Xiao-Xi
authors.initials: XX
authors.lastname: Xu
authors.affiliation: Department of Oncology, The Third People's Hospital of Dalian, Dalian, People's Republic of China.
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Fan
authors.affiliation: Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.affiliation: Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Lu
authors.affiliation: Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, People's Republic of China.
authors.forename: Guang-Wei
authors.initials: GW
authors.lastname: Sun
authors.affiliation: Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, People's Republic of China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Ma
mesh_terms: D000464:Alginates / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005109:Extracellular Matrix / Q000737:chemistry*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D017239:Paclitaxel
keywords: alginate gel (ALG) beads; drug resistance; matrix stiffness; response surface methodology (RSM)