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The Inhibitory Effect of Mesenchymal Stem Cells with rAd-NK4 on Liver Cancer
Chao Cai1, Lingling Hou2, Jingsi Zhang1
1College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, 100044, People's Republic of China.
Abstract:
Mesenchymal stem cells (MSCs) can migrate to the tumor site and integrate into the tumor tissue. As a delivery vehicle of antitumor factors, MSCs have been tried in various tumor therapies. NK4 can both inhibit the growth, metastasis, and invasion of tumor cells induced by hepatocyte growth factor (HGF) and suppress tumor angiogenesis that is independent on HGF/cellular-mesenchymal-to-transition factor pathway. Adenovirus can directly deliver NK4 for tumor treatment but may induce immunological rejection. We combined MSCs with an adenovirus vector to deliver NK4 for liver tumor treatment. This study detected the migration of MSCs to high metastasis liver carcinoma cells MHCC-97H in vitro, investigated the inhibitory effect of rAd-NK4-MSCs on the growth and metastasis of MHCC-97H cells, further explored the inhibitory mechanism of rAd-NK4-MSCs to MHCC-97H cell metastasis, and examined the inhibitory effect of rAd-NK4-MSCs on the migration of human umbilical vein endothelial cells (HUVECs) in vitro. In this study, migration experiment was used for the potential capacity of MSCs and inhibition on migration of rAd-NK4-MSCs. Western blot was used for detecting the inhibition mechanism of rAd-NK4-MSCs to MHCC-97H cells. And, animal transplantation experiment was used for the inhibition of rAd-NK4-MSCs in vivo. MSC migration assay showed MSCs can significantly migrate to MHCC-97H cells. Co-culture results indicated that rAd-NK4-MSCs significantly inhibited the proliferation and migration of MHCC-97H cells in vitro. Western blot results proved that rAd-NK4-MSCs inhibited MHCC-97H cell migration correlating with suppressing Erk1/2 phosphorylation. HUVEC migration experiment suggested that rAd-NK4-MSCs had a potential of inhibiting tumor angiogenesis. Animal transplantation experiment showed that the tumor growth was significantly inhibited in the rAd-NK4-MSC group. Taken together, this study proved that NK4-modified MSCs had an inhibitory effect on the growth and migration of MHCC-97H cells and tumor angiogenesis, which provided a new strategy for liver tumor target therapy.
Insights
Mesenchymal stem cells (MSCs) modified with NK4 show promise in liver cancer therapy. These engineered MSCs effectively inhibit tumor growth, metastasis, and angiogenesis, offering a new targeted treatment strategy.
Area of Science:
- Oncology
- Regenerative Medicine
- Biotechnology
Background:
- Mesenchymal stem cells (MSCs) are explored as delivery vehicles for cancer therapy due to their tumor-homing properties.
- NK4 is a potent inhibitor of tumor growth, metastasis, and angiogenesis.
- Adenovirus vectors can deliver therapeutic genes but may cause immunological rejection.
Purpose of the Study:
- To evaluate the efficacy of NK4-modified MSCs (rAd-NK4-MSCs) as a targeted therapy for liver cancer.
- To investigate the anti-metastatic and anti-angiogenic mechanisms of rAd-NK4-MSCs.
- To assess the in vitro and in vivo therapeutic potential of rAd-NK4-MSCs against MHCC-97H liver carcinoma cells.
Main Methods:
- In vitro migration assays to assess MSC homing to MHCC-97H cells.
- Co-culture experiments to evaluate the effects of rAd-NK4-MSCs on MHCC-97H cell proliferation and migration.
- Western blot analysis to determine the molecular mechanisms of inhibition (Erk1/2 phosphorylation).
- In vitro human umbilical vein endothelial cell (HUVEC) migration assays to assess anti-angiogenic potential.
- In vivo animal transplantation experiments to evaluate tumor growth inhibition.
Main Results:
- MSCs demonstrated significant migration towards MHCC-97H liver carcinoma cells in vitro.
- rAd-NK4-MSCs significantly inhibited MHCC-97H cell proliferation and migration.
- The anti-migratory effect of rAd-NK4-MSCs on MHCC-97H cells was associated with suppressed Erk1/2 phosphorylation.
- rAd-NK4-MSCs showed potential in inhibiting HUVEC migration, suggesting anti-angiogenic activity.
- In vivo studies confirmed significant inhibition of tumor growth in the rAd-NK4-MSC treatment group.
Conclusions:
- NK4-modified MSCs represent a promising targeted therapy for liver cancer, effectively inhibiting tumor growth, migration, and angiogenesis.
- This approach overcomes potential immunological issues associated with direct adenovirus delivery.
- rAd-NK4-MSCs offer a novel and effective strategy for liver tumor treatment.
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