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Efficacy studies of Sclerotium rolfsii lectin on breast cancer using NOD SCID mouse model
Prajna Hegde1, Jagadeesh Narasimhappagari1, Bale M Swamy1
1Department of Studies in Biochemistry, Karnatak University, Dharwad, India.
Abstract:
Expression of altered glycans such as TF, Tn, and sTn antigens has been observed in a number of carcinomas which are targeted in cancer therapy. Sclerotium rolfsii lectin (SRL) is known to recognize TF and its substituted forms. Clinical potential of SRL has been demonstrated by studying its interaction with different types of cancer cells. Here we report, in vitro studies of SRL on breast cancer MDA-MB-468 cells and in vivo studies with MCF-7 xenografts. In vitro growth inhibitory studies of SRL on metastatic triple negative breast cancer MDA-MB-468 cells were performed by MTT assay, flow cytometry, adhesion, and CAM assay. In vivo efficacy studies of SRL were performed using NOD SCID mice bearing MCF-7 xenografts. SRL has strong binding to MDA-MB-468 cells with MFI of 85.5 and has growth inhibitory effect with IC50 of 32 μg/ml at 48 hr. SRL has antiangiogenesis effect and also anti adhesive effect with fibronectin and collagen at 20 μg/ml by 36% and 42%, respectively. In vivo efficacy studies of SRL on NOD SCID mice bearing MCF-7 xenogratfs revealed 61.77% and 75.71% tumor regressing effect, respectively, at 20 and 30 mg/kg body weight without any toxicity. All these results substantiate clinical potential of SRL on breast cancer.
Insights
Sclerotium rolfsii lectin (SRL) shows significant potential in breast cancer therapy by inhibiting tumor growth and angiogenesis. In vitro and in vivo studies demonstrate SRL
Area of Science:
- Biochemistry and Molecular Biology
- Cancer Research
- Pharmacology
Background:
- Altered glycan expression (TF, Tn, sTn antigens) is common in carcinomas and a target for cancer therapy.
- Sclerotium rolfsii lectin (SRL) specifically recognizes TF and its substituted forms, indicating potential therapeutic applications.
- Previous studies have shown SRL's interaction with various cancer cells, suggesting its clinical relevance.
Purpose of the Study:
- To investigate the in vitro and in vivo efficacy of Sclerotium rolfsii lectin (SRL) as a potential therapeutic agent for breast cancer.
- To evaluate SRL's effects on the growth, adhesion, and angiogenesis of breast cancer cells.
- To assess the in vivo anti-tumor activity and toxicity of SRL in a mouse xenograft model.
Main Methods:
- In vitro studies utilized MTT assay, flow cytometry, adhesion assays, and the chick chorioallantoic membrane (CAM) assay on MDA-MB-468 breast cancer cells.
- In vivo efficacy studies were conducted on NOD SCID mice bearing MCF-7 xenografts.
- Binding affinity, growth inhibition (IC50), anti-angiogenesis, and anti-adhesion effects of SRL were quantified.
Main Results:
- SRL exhibited strong binding to MDA-MB-468 cells (MFI of 85.5) and demonstrated significant growth inhibition (IC50 of 32 μg/ml at 48 hr).
- SRL displayed anti-angiogenesis and anti-adhesion effects on fibronectin and collagen (36% and 42% inhibition at 20 μg/ml, respectively).
- In vivo studies showed substantial tumor regression in MCF-7 xenografts (61.77% at 20 mg/kg and 75.71% at 30 mg/kg) with no observed toxicity.
Conclusions:
- These findings strongly support the clinical potential of Sclerotium rolfsii lectin (SRL) in the treatment of breast cancer.
- SRL demonstrates multifaceted anti-cancer properties, including direct growth inhibition, anti-angiogenesis, and anti-adhesion.
- The lack of toxicity in vivo further enhances SRL's promise as a therapeutic candidate for breast cancer.
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