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Andrographolide suppresses cervical cancer progression by targeting angiogenesis and inducing apoptosis in a CAM-PDX
Wanwan Zou1, Jun Lou2, Yun Yi2
1Department of Pathology, Jiangxi Provincial Cancer Hospital, Nanchang, China.
Abstract:
Cervical cancer poses significant clinical challenges, particularly in advanced stages. This study explores the therapeutic potential of andrographolide (AND), a bioactive compound derived from Andrographis paniculata, in mitigating cervical cancer progression using the chick embryo chorioallantoic membrane patient-derived xenograft (CAM-PDX) model. The model was validated through hematoxylin-eosin (H&E) staining and immunohistochemistry, which confirmed its ability to accurately replicate the histological and molecular characteristics of patient-derived xenografts (PDXs), establishing its reliability for therapeutic screening. A dose of 20 mg/kg AND was selected for further evaluation based on preliminary chorioallantoic membrane (CAM) assay findings. In the CAM-PDX model, AND significantly inhibited tumor growth, primarily by reducing angiogenesis and vessel density. Immunohistochemical analysis revealed that AND downregulated key proteins associated with cancer cell proliferation and survival, including Ki67, B-cell lymphoma 2 (BCL-2), and Erythroblast transformation-specific-related gene (ERG). These results indicate that AND not only disrupts tumor angiogenesis but also induces cell cycle arrest and promotes apoptosis in cervical cancer cells. In summary, this study successfully established a reproducible CAM-PDX model for drug evaluation and highlighted the potential of AND as a promising therapeutic candidate for cervical cancer, warranting further clinical investigation.
Insights
Andrographolide (AND) effectively inhibits cervical cancer growth by reducing blood vessel formation and promoting cancer cell death. This study validates a new drug screening model for advanced cervical cancer therapies.
Area of Science:
- Oncology
- Pharmacology
- Biotechnology
Background:
- Cervical cancer presents significant challenges, especially in advanced stages.
- Andrographis paniculata yields andrographolide (AND), a bioactive compound with therapeutic potential.
- Existing treatment models require validation for effective drug screening.
Purpose of the Study:
- To evaluate the therapeutic efficacy of andrographolide (AND) against cervical cancer.
- To establish and validate a chick embryo chorioallantoic membrane patient-derived xenograft (CAM-PDX) model for drug evaluation.
- To investigate the anti-angiogenic and anti-proliferative mechanisms of AND in cervical cancer.
Main Methods:
- Development and validation of a CAM-PDX model using hematoxylin-eosin (H&E) staining and immunohistochemistry.
- Administration of a 20 mg/kg dose of AND in the established CAM-PDX model.
- Assessment of tumor growth, angiogenesis, and protein expression (Ki67, BCL-2, ERG) via immunohistochemistry.
Main Results:
- The CAM-PDX model accurately replicated patient-derived xenograft characteristics, confirming its reliability.
- AND significantly inhibited cervical cancer tumor growth in the CAM-PDX model.
- AND reduced tumor angiogenesis and downregulated key proteins (Ki67, BCL-2, ERG), indicating cell cycle arrest and apoptosis induction.
Conclusions:
- A reproducible CAM-PDX model was successfully established for cervical cancer drug evaluation.
- Andrographolide (AND) demonstrates significant anti-tumor activity by targeting angiogenesis and promoting apoptosis.
- AND shows promise as a therapeutic candidate for cervical cancer, meriting further clinical research.
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