The inhibitory effect of strontium on colorectal cancer and its impact on the gut microbiome.

Colorectal cancer (CRC) is one of the most prevalent malignant tumors worldwide. Strontium (Sr) is an essential trace element in the human body, and Sr compounds have been shown to inhibit the growth of various cancer cell types. However, the mechanism of action of SR in CRC remains unclear. In our previous study, we found that serum Sr levels in patients with CRC were lower than those in the normal population. But its role in CRC development and its influence on the gut microbiome remain unclear. To articulate the mechanism of action of Sr in CRC, we conducted CCK8, plate cloning, cell scratch, and Transwell migration assays. Mitochondrial membrane potential measurements were used to evaluate the effects of Sr on the biological functions of CRC cells. By constructing a nude mouse xenograft model, the pathological changes in CRC tumors and colon tissues, as well as the expression levels of CaSR, Bcl-2, and Caspase-3 proteins, were analyzed. Changes in the gut microbiota were analyzed using 16S rRNA gene sequencing. SrCl2 and SrRan significantly inhibited CRC cell proliferation (P < 0.05), migration (P < 0.05), and invasion (P < 0.001), while inducing G1/S phase arrest and apoptosis mediated by the mitochondrial pathway. Animal experiments demonstrated a 68.60 % reduction in tumor volume in the strontium-treated group, accompanied by a marked downregulation of Ki67 expression. In addition,16S rRNA sequencing revealed that strontium modulated the gut microbiota composition in CRC nude mice, characterized by a significant increase in the relative abundance of Lactobacillus species (P < 0.05). This study suggests that strontium supplementation may provide a theoretical basis for the treatment of colorectal cancer and the optimization of comprehensive treatment strategies for this condition.