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Updated: Jan 29, 2026
Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells
Published on: June 9, 2020
Bazedoxifene as a novel GP130 inhibitor for Colon Cancer therapy
Jia Wei1,2, Ling Ma2, Yi-Hui Lai3
1Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Background:
Interleukin-11 (IL-11), a dominant IL-6 family cytokine, is involved in tumorigenesis, tumor progression and differentiation in colon cancer cells. IL-11 signaling has been recently identified as a potential therapeutic target in colon cancer. Bazedoxifene, a third- generation selective estrogen modulator approved by the Food and Drug Administration (FDA), is a novel inhibitor of IL-11/GP130 signaling discovered by docking modeling.
Methods:
In this study, the inhibition efficacy of bazedoxifene in colon cancer cells and its potential mechanism were investigated in vitro and in vivo by using MTT cell viability assay, BrdU cell proliferation assay, colony formation assay, wound-healing/cell migration assay, immunofluorescence, western blot assay and the mouse xenograft tumor model.
Results:
Bazedoxifene inhibits phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) and its nuclear translocation induced by IL-11 in colon cancer cells. It also inhibits p-STAT3 induced by IL-6 and IL-11 but not by OSM or STAT1 phosphorylation induced by INF-γ in human colon cancer cells. In addition, bazedoxifene can significantly inhibit phosphorylation of AKT and STAT3 downstream targets. Furthermore, bazedoxifene alone or together with oxaliplatin can significantly induce apoptosis, inhibit cell viability, cell colony formation and cell migration in colon cancer cells. Knock-down of IL-11R can reduce the sensitivity of colon cancer cells to bazedoxifene. IL-11 can reduce the efficacy of oxaliplatin-mediated inhibition of cell viability. Consistent with in vitro findings, bazedoxifene alone also attenuated HCT-15 xenograft tumor burden and reduced p-STAT3, p-AKT and p-ERK in vivo. Its combination with oxaliplatin attenuated DLD-1 xenograft tumor burden and reduced p-STAT3 in vivo.
Conclusions:
Taken together, these results support bazedoxifene as a novel and effective therapeutic agent targeting IL-11/GP130 signaling for human colorectal cancer therapy.
Insights
Bazedoxifene effectively inhibits Interleukin-11 (IL-11)/GP130 signaling in colon cancer cells, reducing tumor growth and migration. This drug shows promise as a novel therapeutic agent for colorectal cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Interleukin-11 (IL-11) is a key cytokine in colon cancer progression.
- IL-11 signaling represents a potential therapeutic target for colorectal cancer.
- Bazedoxifene, an FDA-approved selective estrogen modulator, is identified as an IL-11/GP130 signaling inhibitor.
Purpose of the Study:
- To investigate the efficacy of bazedoxifene in inhibiting colon cancer cell growth and its underlying mechanisms.
- To evaluate bazedoxifene's therapeutic potential in both in vitro and in vivo models of colorectal cancer.
Main Methods:
- Utilized MTT, BrdU, colony formation, and wound-healing assays to assess cell viability, proliferation, and migration.
- Employed immunofluorescence and western blot assays to analyze protein phosphorylation and translocation.
- Evaluated bazedoxifene's efficacy in a mouse xenograft tumor model.
Main Results:
- Bazedoxifene inhibited IL-11-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation and nuclear translocation.
- It suppressed STAT3 and AKT phosphorylation, induced apoptosis, and inhibited cell viability, colony formation, and migration.
- In vivo, bazedoxifene reduced tumor burden and key signaling pathway activation in xenograft models.
Conclusions:
- Bazedoxifene demonstrates significant anti-cancer effects in colorectal cancer models.
- The drug effectively targets the IL-11/GP130 signaling pathway.
- Bazedoxifene is a promising novel therapeutic agent for human colorectal cancer.
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