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Updated: Nov 4, 2025
A Simple Method to Identify Kinases That Regulate Embryonic Stem Cell Pluripotency by High-throughput Inhibitor Screening
Published on: May 12, 2017
A high-throughput screen identifies inhibitors of lung cancer stem cells
Xiaofei She1, Yaqun Gao1, Yan Zhao1
1School of Life Sciences and Technology, Cancer Center, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200092, China.
Abstract:
Metastasis is the main cause of cancer morbidity and mortality. Cancer stem cells (CSCs) are a rare subpopulation of cancer cells that can drive metastasis. The identification of CSC inhibitors and CSC-related genes is an alluring strategy for suppressing metastasis. Here, we established a simple and repeatable high-throughput CSC inhibitor screening platform that combined tumor sphere formation assays and cell viability assays. Human lung cancer cells were cocultured with 1280 pharmacologically active compounds (FDA-approved). Fifty-four candidate compounds obtained from our screening system completely or partially inhibited tumor sphere formation. A total of 5 of these 54 compounds (prochlorperazine dimaleate, thioridazine hydrochloride, ciproxifan hydrochloride, Ro 25-6981 hydrochloride, and AMN 082) completely inhibited the self-renewal of CSCs without cytotoxicity in vitro via their targets and suppressed lung cancer metastasis in vivo, suggesting that our screening platform is selective and reliable. DRD2, HRH3, and GRIN2B exhibited potent genes promoting CSCs in vitro experiments and clinical datasets. Further validation of the top hit (DRD2) and previously published studies demonstrate that our screening platform is a useful tool for CSC inhibitor and CSC-related gene screening.
Insights
Researchers developed a high-throughput screening platform to identify cancer stem cell (CSC) inhibitors. Five FDA-approved drugs effectively suppressed lung cancer metastasis by inhibiting CSC self-renewal without cytotoxicity.
Area of Science:
- Oncology
- Cancer Stem Cell Biology
- Drug Discovery
Background:
- Metastasis, driven by cancer stem cells (CSCs), is a primary cause of cancer mortality.
- Targeting CSCs and identifying their regulators are crucial for developing anti-metastasis therapies.
Purpose of the Study:
- To establish a high-throughput screening platform for identifying CSC inhibitors.
- To identify novel CSC inhibitors and CSC-related genes for suppressing metastasis.
Main Methods:
- A platform combining tumor sphere formation and cell viability assays was developed.
- 1280 FDA-approved compounds were screened using human lung cancer cells.
- In vitro and in vivo models were used to validate candidate compounds and identify key genes.
Main Results:
- The screening identified 54 compounds that inhibited tumor sphere formation.
- Five compounds (prochlorperazine dimaleate, thioridazine hydrochloride, ciproxifan hydrochloride, Ro 25-6981 hydrochloride, AMN 082) completely inhibited CSC self-renewal in vitro without cytotoxicity.
- These five compounds suppressed lung cancer metastasis in vivo.
- DRD2, HRH3, and GRIN2B were identified as potent CSC-promoting genes.
Conclusions:
- The developed screening platform is reliable and selective for identifying CSC inhibitors.
- The identified compounds and genes offer potential therapeutic strategies for suppressing cancer metastasis.
- DRD2, HRH3, and GRIN2B are validated as key targets in CSC-driven metastasis.
