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Updated: May 28, 2026
An Orthotopic Resectional Mouse Model of Pancreatic Cancer
Published on: September 24, 2020
STAT3 knockdown reduces pancreatic cancer cell invasiveness and matrix metalloproteinase-7 expression in nude mice
Hai dong Li1, Chen Huang, Ke jian Huang
1Department of General Surgery, Affiliated First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Aims:
Transducer and activator of transcription-3 (STAT3) plays an important role in tumor cell invasion and metastasis. The aim of the present study was to investigate the effects of STAT3 knockdown in nude mouse xenografts of pancreatic cancer cells and underlying gene expression.
Methods:
A STAT3 shRNA lentiviral vector was constructed and infected into SW1990 cells. qRT-PCR and western immunoblot were performed to detect gene expression. Nude mouse xenograft assays were used to assess changes in phenotypes of these stable cells in vivo. HE staining was utilized to evaluate tumor cell invasion and immunohistochemistry was performed to analyze gene expression.
Results:
STAT3 shRNA successfully silenced expression of STAT3 mRNA and protein in SW1990 cells compared to control cells. Growth rate of the STAT3-silenced tumor cells in nude mice was significantly reduced compared to in the control vector tumors and parental cells-generated tumors. Tumor invasion into the vessel and muscle were also suppressed in the STAT3-silenced tumors compared to controls. Collagen IV expression was complete and continuous surrounding the tumors of STAT3-silenced SW1990 cells, whereas collagen IV expression was incomplete and discontinuous surrounding the control tumors. Moreover, microvessel density was significantly lower in STAT3-silenced tumors than parental or control tumors of SW1990 cells. In addition, MMP-7 expression was reduced in STAT3-silenced tumors compared to parental SW1990 xenografts and controls. In contrast, expression of IL-1β and IgT7α was not altered.
Conclusion:
These data clearly demonstrate that STAT3 plays an important role in regulation of tumor growth, invasion, and angiogenesis, which could be act by reducing MMP-7 expression in pancreatic cancer cells.
Insights
Knocking down STAT3 (Signal Transducer and Activator of Transcription-3) significantly inhibited pancreatic cancer growth, invasion, and angiogenesis in mouse models. This suggests STAT3 is a key regulator of tumor progression, potentially by affecting MMP-7 expression.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Signal Transducer and Activator of Transcription-3 (STAT3) is implicated in tumor cell invasion and metastasis.
- Understanding STAT3's role is crucial for developing targeted pancreatic cancer therapies.
Purpose of the Study:
- To investigate the effects of STAT3 knockdown on pancreatic cancer cell xenografts in nude mice.
- To elucidate the underlying gene expression changes associated with STAT3 inhibition.
Main Methods:
- STAT3 knockdown was achieved using a STAT3 shRNA lentiviral vector in SW1990 pancreatic cancer cells.
- Gene and protein expression were analyzed via qRT-PCR and Western immunoblot.
- In vivo efficacy was assessed using nude mouse xenograft models, with histological analysis (HE staining, immunohistochemistry) for invasion and gene expression.
Main Results:
- STAT3 knockdown significantly reduced tumor growth rate, invasion (vessel, muscle), and microvessel density in xenografts.
- STAT3 silencing led to continuous Collagen IV expression around tumors and reduced MMP-7 expression.
- Tumor angiogenesis was suppressed, while IL-1β and IgT7α expression remained unchanged.
Conclusions:
- STAT3 plays a critical role in regulating pancreatic tumor growth, invasion, and angiogenesis.
- STAT3 inhibition, potentially via MMP-7 downregulation, offers a therapeutic strategy for pancreatic cancer.
- Targeting STAT3 could impede pancreatic cancer progression and metastasis.
