Related Experiment Video
Updated: Oct 22, 2025
Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
Published on: June 9, 2023
Vitamin D suppressed gastric cancer cell growth through downregulating CD44 expression in vitro and in vivo
Qianxiu Li1, Yifan Li1, Houxiang Jiang2
1Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Sichuan, China; South Sichuan Institute of Translational Medicine, Sichuan, China.
Objectives:
Vitamin D deficiency was found to be associated with increased risk for gastric cancer (GC). We previously found that vitamin D inhibited GC cell growth in vitro. However, the in vivo antitumor effect of vitamin D in GC as well as the underlying mechanisms are not well understood. The aim of this study was to investigate the anticancer effect of vitamin D on GC both in vitro and in vivo.
Methods:
Human GC cells MKN45, MKN28, and KATO III were used. The expressions of vitamin D receptor (VDR) and CD44 were downregulated by using predesigned siRNA molecules. Cell viability was evaluated by methyl thiazolyl tetrazolium assay. Soft agar assay was used for colony formation of GC cells. Flow cytometry was used to assess CD44-positive cell population. CD44high cancer cells were enriched by using anti-CD44-conjugated magnetic microbeads. Quantitative real-time polymerase chain reaction and Western blot were performed to detect gene and protein expressions, respectively. Clinical samples were collected for evaluation of the correlation of VDR and CD44 expression. Orthotopic tumor-bearing mice were established to evaluate the antitumor effect of vitamin D.
Results:
The results showed that the active form of vitamin D, 1,25(OH)2D3, had a remarkable inhibitory effect in CD44-expressing human GC MKN45 and KATO III cells, but not in CD44-null MKN28 cells. The gene expressions of CD44 and VDR in GC cell lines and GC patient tissues were positively correlated. Furthermore, 1,25(OH)2D3 suppressed MKN45 and KATO III cell growth through VDR-induced suppression of CD44. Additionally, we demonstrated that 1,25(OH)2D3 inhibited Wnt/β-catenin signaling pathway, which might lead to the downregulation of CD44. In an orthotopic GC nude mice model, both oral intake of vitamin D and intraperitoneal injection with 1,25(OH)2D3 could significantly inhibit orthotopic GC growth and CD44 expression in vivo.
Conclusion:
To our knowledge, this study provided the first evidence that vitamin D suppressed GC cell growth both in vitro and in vivo through downregulating CD44. The present study sheds light on repurposing vitamin D as a potential therapeutic agent for GC prevention and treatment.
Insights
Vitamin D effectively inhibits gastric cancer (GC) cell growth by downregulating CD44 expression, both in laboratory studies and in animal models. This research suggests vitamin D could be a potential therapeutic agent for GC prevention and treatment.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Vitamin D deficiency is linked to increased gastric cancer (GC) risk.
- Previous in vitro studies showed vitamin D inhibits GC cell growth.
- The in vivo antitumor effects and mechanisms of vitamin D in GC require further investigation.
Purpose of the Study:
- To investigate the anticancer effects of vitamin D on gastric cancer (GC) cells in vitro and in vivo.
- To elucidate the underlying mechanisms of vitamin D's action in GC.
- To explore the correlation between vitamin D receptor (VDR) and CD44 expression in GC.
Main Methods:
- Utilized human GC cell lines (MKN45, MKN28, KATO III) and clinical samples.
- Assessed cell viability, colony formation, and CD44 expression using MTT, soft agar, and flow cytometry.
- Investigated gene and protein expression via quantitative PCR and Western blot.
- Established orthotopic GC nude mice models to evaluate in vivo antitumor effects.
Main Results:
- The active form of vitamin D, 1,25(OH)2D3, inhibited growth in CD44-expressing GC cells (MKN45, KATO III) but not CD44-null cells (MKN28).
- Positive correlation observed between CD44 and VDR gene expression in GC cell lines and patient tissues.
- 1,25(OH)2D3 suppressed GC cell growth by downregulating CD44 via VDR, potentially through inhibition of the Wnt/β-catenin pathway.
- In vivo, vitamin D significantly inhibited orthotopic GC growth and reduced CD44 expression in mice.
Conclusions:
- This study provides the first evidence that vitamin D suppresses GC cell growth in vitro and in vivo by downregulating CD44.
- Vitamin D's mechanism involves VDR-induced suppression of CD44, potentially linked to the Wnt/β-catenin pathway.
- Repurposing vitamin D presents a potential strategy for GC prevention and treatment.
More Related Videos
Related Concept Videos
02:34Inhibition of Cdk Activity
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
02:59Cancer Prevention
Some...