Study summary · research use only
Raloxifene and antiestrogenic gonadorelin inhibits intestinal tumorigenesis by modulating immune cells and decreasing stem-like cells
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this study using female Apc(Min/+) mice, the authors examined raloxifene, a selective estrogen receptor modulator, and gonadorelin, an antiestrogenic drug, on intestinal tumorigenesis. Mice were fed diet with 1 ppm raloxifene or control diet, and one group was injected subcutaneously with gonadorelin (150 ng/mouse). The abstract reports colon tumor inhibition of 80% and 75% with raloxifene and gonadorelin respectively, significant reduction of small-intestinal tumor multiplicity and size (75%-65%), and 98% and 94% inhibition of polyps larger than 2 mm. Both agents reduced proliferating cell nuclear antigen expression (58%-65%) and modulated stem-like cell and inflammatory gene markers, by different mechanisms.
Abstract
Studies suggest that estrogen plays a contributing role in colorectal cancer. This project examined the preventive effects of raloxifene, a selective estrogen receptor modulator (SERM), and gonadorelin, an antiestrogenic drug, in female Apc(Min/+) mouse intestinal tumorigenesis. Six-week-old Apc(Min/+)mice were fed diet containing 1 ppm raloxifene or control diet. Gonadorelin (150 ng/mouse) was injected subcutaneously into one treatment group. Intestinal tumors were evaluated for tumor multiplicity and size. Mice treated with raloxifene and gonadorelin showed colon tumor inhibition of 80% and 75%, respectively. Both drugs significantly inhibited small intestinal tumor multiplicity and size (75%-65%, P < 0.0001). Raloxifene and gonadorelin showed significant tumor inhibition with 98% and 94% inhibition of polyps >2 mm in size. In mice fed with raloxifene or injected with gonadorelin, tumors showed significantly reduced proliferating cell nuclear antigen expression (58%-65%, P < 0.0001). Raloxifene treatment decreased β-catenin, cyclin D1, laminin 1β, Ccl6, and stem-like cells (Lgr 5, EpCAM, CD44/CD24), as well as suppressed inflammatory genes (COX-2, mPGES-1, 5-LOX,). Gonadorelin showed significant decrease in COX-2, mPGES-1, iNOS, and stem-like cells or increased NK cells and chemokines required for NK cells. Both drugs were effective in suppressing tumor growth albeit with different mechanisms. These observations show that either suppression of estrogen levels or modulation of estrogen receptor dramatically suppresses small intestinal and colonic tumor formation in female Apc(Min/+) mice. These results support the concept of chemoprevention by these agents in reducing endogenous levels of estrogen or modulating ER signaling.
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