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Integrated transcriptomic and proteomic analysis reveals Guizhi-Fuling Wan inhibiting STAT3-EMT in ovarian cancer
Qihong Ma1, Fangfang Chen1, Ying Liu1
1School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China.
Background:
Ovarian cancer (OC) is the most lethal gynecological malignancy. Frequent peritoneal dissemination is the main cause of low survival rate. Guizhi-Fuling Wan (GZFL) is a classical traditional Chinese herbal formula that has been clinically used for treating ovarian cancer with good outcome. However, its therapeutic mechanism for treating OC has not been clearly elucidated.
Purpose:
We aim to elucidate the potential mechanisms of GZFL in treating OC with a focus on STAT3 signaling pathway.
Methods:
In vivo efficacy of GZFL was assessed using an OC xenograft mouse model. Proteomics analysis in OC cells and RNA-seq analysis in mice tumors were performed to fully capture the translational and transcriptional signature of GZFL. Effects of GZFL on proliferation, spheroid formation and reactive oxygen species (ROS) were assessed using wildtype and STAT3 knockout OC cells in vitro. STAT3 activation and transcription activity, hypoxia and EMT-related protein expression were assessed to validate the biological activity of GZFL.
Results:
GZFL suppresses tumor growth with a safety profile in mice, while prevents cell growth, spheroid formation and accumulates ROS in a STAT3-dependent manner in vitro. GZFL transcriptionally and translationally affects genes involved in inflammatory signaling, EMT, cell migration, and cellular hypoxic stress response. In depth molecular study confirmed that GZFL-induced cytotoxicity and EMT suppression in OC cells are directly corelated to inhibition of STAT3 activation and transcription activity.
Conclusion:
Our study provides the first evidence that GZFL inhibits OC progression through suppressing STAT3-EMT signaling. These results will further support its potential clinical use in OC.
Insights
Guizhi-Fuling Wan (GZFL) suppresses ovarian cancer (OC) growth by inhibiting the STAT3 signaling pathway. This traditional Chinese medicine reduces cell proliferation and metastasis, supporting its clinical use for OC treatment.
Area of Science:
- Gynecological Oncology
- Traditional Chinese Medicine
- Molecular Biology
Background:
- Ovarian cancer (OC) is a lethal gynecological malignancy with poor survival rates, primarily due to peritoneal dissemination.
- Guizhi-Fuling Wan (GZFL), a traditional Chinese herbal formula, shows clinical efficacy in treating OC, but its mechanisms remain unclear.
Purpose of the Study:
- To elucidate the therapeutic mechanisms of GZFL in ovarian cancer, focusing on the STAT3 signaling pathway.
- To investigate the effects of GZFL on OC progression and related molecular pathways.
Main Methods:
- Assessed in vivo efficacy of GZFL using an OC xenograft mouse model.
- Performed proteomics and RNA-seq analyses to identify GZFL's molecular targets.
- Evaluated GZFL's effects on cell proliferation, spheroid formation, and reactive oxygen species (ROS) in wildtype and STAT3 knockout OC cells.
Main Results:
- GZFL suppressed tumor growth in vivo and inhibited OC cell proliferation, spheroid formation, and increased ROS in vitro, dependent on STAT3.
- GZFL affected genes involved in inflammatory signaling, epithelial-mesenchymal transition (EMT), cell migration, and hypoxic stress.
- GZFL-induced cytotoxicity and EMT suppression were directly correlated with STAT3 inhibition.
Conclusions:
- GZFL inhibits ovarian cancer progression by suppressing the STAT3-EMT signaling pathway.
- This study provides evidence supporting the potential clinical application of GZFL for ovarian cancer treatment.
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