8-bromo-7-methoxychrysin suppress stemness of SMMC-7721 cells induced by co-culture of liver cancer stem-like cells with hepatic stellate cells

Autor: Yinghong Cui, Meifang Quan, Jianguo Cao, Kaiqun Ren, Chang Xu, Nuo-Min Liu, Qi Wen, Jie Zhou
Rok vydání: 2019
Předmět:
0301 basic medicine
Cancer Research
Carcinoma
Hepatocellular
Mice
Nude
Interleukin 6
lcsh:RC254-282
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Downregulation and upregulation
Cancer stem cell
Cell Line
Tumor
Hepatic Stellate Cells
Genetics
medicine
Animals
Humans
Chrysin
Fibroblast
Flavonoids
Hepatocyte growth factor
Mice
Inbred BALB C
Hepatocellular carcinoma
liver cancer stem cell
Dose-Response Relationship
Drug
biology
Interleukin-6
Interleukin-8
Liver Neoplasms
CD44
8-bromo-7-methoxychrysin
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Xenograft Model Antitumor Assays
Coculture Techniques
030104 developmental biology
medicine.anatomical_structure
Oncology
chemistry
Cell culture
030220 oncology & carcinogenesis
Neoplastic Stem Cells
Hepatic stellate cell
Cancer research
biology.protein
Female
Platelet-derived growth factor receptor
Research Article
Zdroj: BMC Cancer, Vol 19, Iss 1, Pp 1-12 (2019)
BMC Cancer
ISSN: 1471-2407
DOI: 10.1186/s12885-019-5419-5
Popis: Background Our previous works have demonstrated that 8-bromo-7-methoxychrysin suppressed stemness of human hepatocellular carcinoma (HCC) cell line SMMC-7721 induced by condition medium from hepatic stellate cell line LX-2 that was activated by liver cancer stem-like cells (LCSCs). However, whether and whereby BrMC inhibits the stemness induced by co-culture of LCSCs and LX-2 cells remains to be investigated. Methods The second-generation spheres by sphere culture were identified and used as SMMC-7721-and MHCC97H-derived LCSLCs. SMMC-7721-and MHCC97-derived LCSCs/LX-2 cells transwell co-culture system was treated with BrMC and its lead compound chrysin. The concentrations of IL-6, IL-8, HGF and PDGF in condition medium from co-culture were measured by enzyme-linked immunosorbent assay (ELISA). The stemness of SMMC-7721 cells was evaluated by sphere formation assay and western blot analysis for expression levels of cancer stem cell markers (CD133 and CD44).The expression levels of cancer-associated fibroblast markers (FAP-α and α-SMA) were employed to evaluate pathologic activation of LX-2 cells. Addition of IL-6 and/or HGF or deletion of IL-6 and/or HGF was conducted to investigate the mechanisms for BrMC and chrysin treatment in SMMC-7721-derived LCSLCs co-cultured with LX-2cells. Results The co-culture of LCSLCs with LX-2 cells increased sphere formation capability as well as expression of CD133 and CD44 in SMMC-7721 cells, meanwhile, upregulated expression of FAP-α in LX-2 cells. ELISA indicated that the concentrations of IL-6 and HGF were significantly elevated in Co-CM than that of condition media from co-cultured SMMC-7721 cells/LX-2 cells. Treatment of BrMC and chrysin with co-cultures of SMMC-7721- and MHCC97H-derived LCSLCs and LX-2 cells effectively inhibited the above responses. Moreover, addition of IL-6 and/or HGF induced stemness of SMMC-7721 cells and activation of LX-2 cells, conversely, deletion of IL-6 and/or HGF suppressed those. Furthermore, the inhibitory effects of BrMC and chrysin on stemness of SMMC-7721 cells and activation of LX-2 cells were attenuated by addition of IL-6 or HGF, and enhanced by deletion of IL-6 or HGF. Conclusions Our results suggest IL-6 and HGF may be the key communication molecules for the interaction between LCSLCs and HSCs, and BrMC and chrysin could block these effects and be the novel therapeutic candidates for HCC management.
Databáze: OpenAIRE
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