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Modulation of the gamma-secretase activity as a therapy against human hepatocellular carcinoma

Yuqing Shen1, Ying Yin2, Yaqin Peng1

  • 1Department of Microbiology and Immunology, Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Medical School, Southeast University, Nanjing, Jiangsu Province, China.

Journal of Cancer Research and Therapeutics
|July 5, 2018
PubMed
Abstract

Insights

Gamma secretase inhibitors (GSIs) show promise for treating hepatocellular carcinoma (HCC). This study found that inhibiting gamma secretase activity reduced HCC cell growth and colony formation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Hepatocellular carcinoma (HCC) is a significant global health concern.
  • Identifying novel therapeutic targets is crucial for advancing HCC treatment.
  • Gamma-secretase (γ-secretase) plays a role in cancer development.

Purpose of the Study:

  • To investigate the activity of γ-secretase in HCC.
  • To evaluate the antitumor effects of γ-secretase inhibitors (GSIs) in HCC models.

Main Methods:

  • Western blot analysis was used to assess presenilin 1 (PS1) expression.
  • A luciferase reporter system measured γ-secretase activity.
  • HCC cells were treated with a GSI or transfected with a PS1 dominant-negative mutant.

Main Results:

  • PS1 expression and γ-secretase activity were elevated in HCC tissues and cell lines.
  • GSI treatment significantly decreased HCC cell colony formation and proliferation.
  • PS1 dominant-negative mutant transfection did not affect cell growth.

Conclusions:

  • Elevated γ-secretase activity is associated with HCC.
  • GSIs demonstrate potential as a therapeutic strategy for HCC.
  • Targeting γ-secretase warrants further investigation for HCC treatment.
Keywords:
Cell proliferationgamma-secretasehepatocellular carcinomaliverpresenilin 1

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