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Updated: May 21, 2026
Portal Vein Injection of Colorectal Cancer Organoids to Study the Liver Metastasis Stroma
Published on: September 3, 2021
Hepatic vitamin A preloading reduces colorectal cancer metastatic multiplicity in a mouse xenograft model
Eun Young Park1, Daniel Pinali, Krista Lindley
1School of Family and Consumer Sciences, Nutrition and Foods Program, Texas State University-San Marcos, San Marcos, Texas 78666, USA.
Abstract:
Previous research in our laboratory showed that retinol inhibited all-trans retinoic acid (ATRA)-resistant human colon cancer cell invasion via a retinoic acid receptor-independent mechanism in vitro. The objective of the current study was to determine if dietary vitamin A supplementation inhibited metastasis of ATRA-resistant colon cancer cells in a nude mouse xenograft model. Female nude mice (BALB/cAnNCr-nu/nu, n = 14 per group) consumed a control diet (2,400 IU retinyl palmitate/kg diet) or a vitamin A supplemented diet (200,000 IU retinyl palmitate/kg diet) for 1 mo prior to tumor cell injection to preload the liver with vitamin A. HCT-116, ATRA-resistant, human colon cancer cells were intrasplenically injected. Mice continued to consume their respective diets for 5 wk following surgery. Consumption of supplemental vitamin A decreased hepatic metastatic multiplicity to 17% of control. Hepatic and splenic retinol and retinyl ester concentrations were significantly higher in the mice supplemented with vitamin A when compared to mice consuming the control diet. Supplemental vitamin A did not decrease body weight, feed intake, or cause toxicity. Thus, supplemental dietary vitamin A may decrease the overall number of hepatic metastasis resulting from colon cancer.
Insights
Dietary vitamin A supplementation significantly reduced colon cancer metastasis in mice. High vitamin A intake decreased liver metastasis without causing toxicity, suggesting a potential therapeutic role.
Area of Science:
- Oncology
- Nutritional Science
- Cancer Metastasis Research
Background:
- Previous studies indicated retinol inhibits all-trans retinoic acid (ATRA)-resistant colon cancer cell invasion in vitro.
- The mechanism of inhibition was found to be independent of the retinoic acid receptor.
Purpose of the Study:
- To investigate the in vivo efficacy of dietary vitamin A supplementation in preventing metastasis of ATRA-resistant human colon cancer cells.
- To evaluate the impact of high-dose vitamin A on metastasis in a nude mouse xenograft model.
Main Methods:
- Female nude mice were fed either a control or a vitamin A-supplemented diet for one month prior to intrasplenic injection of ATRA-resistant HCT-116 colon cancer cells.
- Mice continued the respective diets for five weeks post-injection, with liver and spleen tissues analyzed for vitamin A concentrations and metastatic burden.
Main Results:
- Supplemental vitamin A significantly reduced hepatic metastatic multiplicity by 83% compared to the control group.
- Mice on the supplemented diet exhibited significantly higher hepatic and splenic retinol and retinyl ester concentrations.
- No significant decrease in body weight, feed intake, or signs of toxicity were observed in the supplemented group.
Conclusions:
- Dietary vitamin A supplementation effectively inhibits the metastasis of ATRA-resistant colon cancer in a preclinical mouse model.
- High-dose vitamin A appears to be a safe and potentially effective strategy for reducing colon cancer liver metastasis.
