1. Academic Validation
  2. β1 integrin-mediated multicellular resistance in hepatocellular carcinoma through activation of the FAK/Akt pathway

β1 integrin-mediated multicellular resistance in hepatocellular carcinoma through activation of the FAK/Akt pathway

  • J Int Med Res. 2018 Apr;46(4):1311-1325. doi: 10.1177/0300060517740807.
Tao Tian 1 Chun-Li Li 1 Xiao Fu 1 Shu-Hong Wang 1 Jun Lu 2 Hui Guo 1 Yu Yao 1 Ke-Jun Nan 1 Yu-Juan Yang 3
Affiliations

Affiliations

  • 1 1 Department of Oncology, 162799 First Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, China.
  • 2 2 Clinical Research Centre, 162799 First Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, China.
  • 3 3 Third Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi Province, China.
Abstract

Objective To explore the role and mechanism of β1 Integrin in the regulation of multicellular drug resistance in hepatocellular carcinoma (HCC). Methods This in vitro study used a liquid overlay technique to obtain multicellular spheroids of two human HCC cell lines, HepG2 and Bel-7402. The morphology of the spheroids was observed by optical and electron microscopy. The effects of exposure to 5-fluorouracil (5-FU) and cisplatin (CDDP) on cell proliferation and the induction of Apoptosis were assessed in monolayer cells and multicellular spheroids. The levels of β1 Integrin and the effects on the focal adhesion kinase (FAK)/protein kinase B (Akt) pathway were evaluated using Western blot analysis, immunofluorescence and flow cytometry. The role of β1 Integrin was confirmed by using an inhibitory antibody. Results Cell proliferation inhibition and cell Apoptosis induced by 5-FUl and CDDP were abrogated in multicellular spheroids compared with monolayer cells. There were high levels of β1 Integrin in multicellular spheroids. β1 Integrin inhibitory antibody prevented the formation of multicellular spheroids, coupled with a significant increase in proliferation inhibition and Apoptosis induction. β1 Integrin inhibitory antibody effectively suppressed activation of both FAK and Akt in multicellular spheroids. Conclusions β1 Integrin mediated multicellular drug resistance through the FAK/Akt pathway in HCC spheroids.

Keywords

focal adhesion kinase; hepatocellular carcinoma; multicellular resistance; protein kinase B; β1 integrin.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12289
    99.87%, FAK Inhibitor
    FAK