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Isoliquiritigenin Inhibits Gastric Cancer Stemness, Modulates Tumor Microenvironment, and Suppresses Tumor Growth through Glucose-Regulated Protein 78 Downregulation
Chemotherapy is the treatment of choice for gastric cancer; however, the currently available therapeutic drugs for treatment have limited efficacy. Cancer stemness and the tumor microenvironment may play crucial roles in tumor growth and chemoresistance. Glucose-regulated protein 78 (GRP78) is an en...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220208/ https://www.ncbi.nlm.nih.gov/pubmed/35740372 http://dx.doi.org/10.3390/biomedicines10061350 |
Sumario: | Chemotherapy is the treatment of choice for gastric cancer; however, the currently available therapeutic drugs for treatment have limited efficacy. Cancer stemness and the tumor microenvironment may play crucial roles in tumor growth and chemoresistance. Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum chaperone facilitating protein folding and cell homeostasis during stress and may participate in chemoresistance. Isoliquiritigenin (ISL) is a bioactive flavonoid found in licorice. In this study, we demonstrated the role of GRP78 in gastric cancer stemness and evaluated GRP78-mediated stemness inhibition, tumor microenvironment regulation, and chemosensitivity promotion by ISL. ISL not only suppressed GRP78-mediated gastric cancer stem cell–like characteristics, stemness-related protein expression, and cancer-associated fibroblast activation but also gastric tumor growth in xenograft animal studies. The findings indicated that ISL is a promising candidate for clinical use in combination chemotherapy. |
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