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Isoliquiritigenin Inhibits Gastric Cancer Stemness, Modulates Tumor Microenvironment, and Suppresses Tumor Growth

Chien-Hsing Lee1,2,3,4, Hsin-Yi Tsai5,6, Chun-Lin Chen7

  • 1Department of Pharmacology, School of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

Biomedicines
|June 24, 2022
PubMed

Insights

Isoliquiritigenin (ISL) combats gastric cancer by inhibiting cancer stemness and regulating the tumor microenvironment. This flavonoid enhances chemotherapy efficacy, offering a promising approach for clinical treatment.

Area of Science:

  • Oncology
  • Cancer Biology
  • Pharmacology

Background:

  • Chemotherapy for gastric cancer has limited efficacy, potentially due to cancer stemness and the tumor microenvironment.
  • Glucose-regulated protein 78 (GRP78), an endoplasmic reticulum chaperone, is implicated in chemoresistance.
  • Isoliquiritigenin (ISL), a flavonoid from licorice, has bioactive properties.

Purpose of the Study:

  • To investigate the role of GRP78 in gastric cancer stemness.
  • To evaluate the effects of ISL on GRP78-mediated stemness, tumor microenvironment, and chemosensitivity.
  • To assess ISL's potential as a therapeutic agent for gastric cancer.

Main Methods:

  • Evaluation of GRP78's role in gastric cancer stemness.
  • Assessment of ISL's impact on GRP78-mediated stemness inhibition, tumor microenvironment regulation, and chemosensitivity.
  • Xenograft animal studies to evaluate gastric tumor growth inhibition by ISL.

Main Results:

  • ISL suppressed GRP78-mediated gastric cancer stem cell-like characteristics and stemness-related protein expression.
  • ISL inhibited cancer-associated fibroblast activation and reduced gastric tumor growth in vivo.
  • ISL demonstrated potential in regulating the tumor microenvironment and enhancing chemosensitivity.

Conclusions:

  • ISL effectively targets GRP78-mediated cancer stemness and modulates the tumor microenvironment in gastric cancer.
  • ISL exhibits anti-tumor activity and enhances chemosensitivity, suggesting a role in overcoming chemoresistance.
  • ISL is a promising candidate for combination chemotherapy in clinical settings for gastric cancer treatment.
Keywords:
GRP78cancer stemnesschemosensitivitygastric cancerisoliquiritigenintumor microenvironment

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