Related Experiment Video
Updated: Mar 17, 2026
Enrichment for Chemoresistant Ovarian Cancer Stem Cells from Human Cell Lines
Published on: September 10, 2014
GSK-3 inhibition overcomes chemoresistance in human breast cancer
Andrey Ugolkov1, Irina Gaisina2, Jin-San Zhang3
1Center for Developmental Therapeutics, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, 2170 Campus Drive, Evanston, IL 60208, USA; Division of Hematology Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Galter Suite 3-150, 251 East Huron Street, Chicago, IL 60611, USA; Chemistry of Life Processes Institute, Northwestern University, 2170 Campus Drive, Evanston, IL, 60208, USA.
Abstract:
Glycogen Synthase Kinase-3β (GSK-3β), a serine/threonine protein kinase, is an emerging therapeutic target in the treatment of human breast cancer. In this study, we demonstrate that the pharmacological inhibition of GSK-3 by two novel small molecule GSK-3 inhibitors, 9-ING-41 and 9-ING-87, reduced the viability of breast cancer cells but had little effect on non-tumorigenic cell growth. Moreover, treatment with 9-ING-41 enhanced the antitumor effect of irinotecan (CPT-11) against breast cancer cells in vitro. We next established two patient-derived xenograft tumor models (BC-1 and BC-2) from metastatic pleural effusions obtained from patients with progressive, chemorefractory breast cancer and demonstrated that 9-ING-41 also potentiated the effect of the chemotherapeutic drug CPT-11 in vivo, leading to regression of established BC-1 and BC-2 tumors in mice. Our results suggest that the inhibition of GSK-3 is a promising therapeutic approach to overcome chemoresistance in human breast cancer, and identify the GSK-3 inhibitor 9-ING-41 as a candidate targeted agent for metastatic breast cancer therapy.
Insights
Novel GSK-3 inhibitors, including 9-ING-41, reduce breast cancer cell viability. This inhibitor also enhances chemotherapy effectiveness, offering a promising strategy for chemoresistant metastatic breast cancer.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Glycogen Synthase Kinase-3β (GSK-3β) is a key protein kinase implicated in human breast cancer.
- Targeting GSK-3β presents a novel therapeutic avenue for breast cancer treatment.
Purpose of the Study:
- To evaluate the efficacy of novel small molecule GSK-3 inhibitors (9-ING-41 and 9-ING-87) in breast cancer.
- To investigate the potential of GSK-3 inhibition to overcome chemoresistance in breast cancer.
Main Methods:
- Pharmacological inhibition of GSK-3 using novel small molecules 9-ING-41 and 9-ING-87.
- Assessment of cell viability in breast cancer and non-tumorigenic cell lines.
- In vitro and in vivo studies combining 9-ING-41 with irinotecan (CPT-11).
- Establishment of patient-derived xenograft (PDX) models (BC-1 and BC-2) from metastatic breast cancer.
Main Results:
- GSK-3 inhibitors 9-ING-41 and 9-ING-87 selectively reduced breast cancer cell viability.
- 9-ING-41 demonstrated synergistic antitumor effects when combined with CPT-11 in vitro.
- In vivo studies showed that 9-ING-41 potentiated CPT-11 efficacy, leading to tumor regression in BC-1 and BC-2 xenografts.
Conclusions:
- GSK-3 inhibition is a viable strategy to combat chemoresistance in human breast cancer.
- The GSK-3 inhibitor 9-ING-41 shows potential as a targeted therapy for metastatic breast cancer, particularly in combination with chemotherapy.
Related Concept Videos
02:56Treatment Resistant Cancers
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...