The combination of phosphoinositol with inositol suppresses colorectal cancer growth and metastasis by regulating CLDN23/ RhoA /ROCK1 pathway

Abstract

Colorectalcancerisa prevalentmalignanttumor, with liver metastases being the primary cause of death. The combination of inositol hexaphosphate (IP6) and inositol (INS) has been shown to inhibit colorectal cancer metastasis.We identified a correlation between CLDN23 expression and the occurrence of liver metastases in colorectal cancer patients. Following the transfection with the lentiviral vector (LV-CLDN23-RNAi), proteomic analysis of SW620 revealed significant alterations in the occludin, ZO-1, RhoA, and ROCK-1 genes expression by western blotting. We found that both SW620 and SW480 cells showed inhibited proliferation, invasion, and migration ability after the treatment with IP6 and INS. Additionally, this combination upregulated occludin and ZO-1, while downregulated CLDN23, RhoA, ROCK-1, and p-MLC2. In conclusion, the combination of IP6 and INS suppressed the proliferation, invasion, and migration of colorectal cancer cells and regulated CLDN23 expression by enhancing tightjunction proteins, such as occludin and ZO1, via the RhoA /ROCK1 pathway.