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Updated: Jul 26, 2025
Mesenchymal Stem Cell Isolation from Pulp Tissue and Co-Culture with Cancer Cells to Study Their Interactions
Published on: January 7, 2019
Human embryonic stem cells exert antitumor effects on prostate cancer cells in a co-culture microenvironment
Xinyue Yang1,2, Yang Lu1,2, Qin Kuang1,2
1Key Laboratory of Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, China.
Abstract:
Prostate cancer is currently the most common malignancy among men. Given the limitations of current conventional anticancer therapies, new high-risk treatments are urgently needed. Previous studies have shown that embryonic stem cells (ESCs) can reverse the tumorigenic phenotype of tumor cells. However, there are still challenges in using human ESCs (hESCs) directly in cancer treatment. To facilitate the practical application of hESCs, we established a co-culture system consisting of prostate cancer cell lines and hESCs and investigated the antitumor activity of the supernatant of the co-culture system (Co-Sp) in vitro and in vivo, as well as the underlying mechanisms involved. The Co-Sp decreased the viability of prostate cancer cells in a concentration-dependent manner, significantly inhibited colony formation, and induced cell cycle arrest at the G0/G1 phase of the cell cycle. In addition, Co-Sp promoted apoptosis of prostate cancer cells and inhibited cell migration and invasion. In vivo studies also revealed that Co-Sp inhibited tumor growth in the xenograft model. Mechanistic studies showed that Co-Sp reduced the expression of cyclin D1, cyclin E, CDK4, CDK2, MMP-9, MMP-1, and Bcl-2, and increased the expression of p21, cleaved caspase-9, cleaved caspase-3, cleaved PARP, and Bax in prostate cancer cells. Furthermore, the Co-Sp decreased the phosphorylation of PI3K, AKT, and mTOR in cells and tumor tissues. Taken together, our results indicated that the Co-Sp has potent antitumor activity and could directly inhibit tumor growth. Our findings provide a new and effective way for the application of hESCs in cancer therapy and contribute to a new strategy for clinical stem cell therapy.
Insights
Supernatant from co-cultured human embryonic stem cells (hESCs) and prostate cancer cells shows potent anti-tumor effects. This novel approach inhibits cancer cell viability, migration, and growth, offering a new strategy for prostate cancer therapy.
Area of Science:
- Oncology
- Stem Cell Biology
- Biotechnology
Background:
- Prostate cancer is the most common male malignancy, with current therapies facing limitations.
- Human embryonic stem cells (hESCs) show potential in reversing tumor cell phenotypes.
- Direct clinical application of hESCs faces challenges, necessitating alternative strategies.
Purpose of the Study:
- To investigate the anti-tumor activity of a co-culture supernatant (Co-Sp) derived from prostate cancer cell lines and hESCs.
- To evaluate the efficacy of Co-Sp both in vitro and in vivo.
- To elucidate the underlying molecular mechanisms of Co-Sp's anti-tumor effects.
Main Methods:
- Established a co-culture system of prostate cancer cell lines and hESCs.
- Assessed Co-Sp's effects on cancer cell viability, colony formation, cell cycle, apoptosis, migration, and invasion in vitro.
- Evaluated Co-Sp's anti-tumor efficacy in a prostate cancer xenograft model in vivo.
- Analyzed molecular changes in key proteins and signaling pathways (e.g., apoptosis markers, cell cycle regulators, PI3K/AKT/mTOR pathway).
Main Results:
- Co-Sp significantly reduced prostate cancer cell viability, inhibited colony formation, and induced G0/G1 cell cycle arrest.
- Co-Sp promoted apoptosis and suppressed migration and invasion of cancer cells.
- In vivo studies demonstrated that Co-Sp inhibited tumor growth in xenograft models.
- Mechanistic studies revealed Co-Sp modulates expression of key proteins involved in cell cycle, apoptosis, and metastasis, and inhibits PI3K/AKT/mTOR signaling.
Conclusions:
- The supernatant from hESC-prostate cancer co-cultures exhibits potent direct anti-tumor activity against prostate cancer.
- Co-Sp effectively inhibits cancer cell proliferation, induces apoptosis, and suppresses metastasis.
- This study presents a novel and effective application of hESCs for prostate cancer therapy, suggesting a promising clinical strategy.
