Objective To explore the mechanism of tubeimoside II (TUB-II) in inhibiting the growth and metastasis of colorectal cancer. Methods Human colorectal cancer cell lines RKO and SW620 were used as research subjects, the effect of TUB-II on viability of RKO and SW620 cells was detected. The cell proliferation ability was detected by colony formation assay. The cell migration ability was detected by scratch assay. Western blotting was used to detect the effect of TUB-II on expressions of lethal (2) giant larvae homolog 2 (LLGL2) and epithelial-mesenchymal transition (EMT)-related proteins in RKO and SW620 cells. Co-immunoprecipitation was used to detect the effect of TUB-II on ubiquitination of LLGL2. Subcutaneous tumor model and colorectal cancer lung metastasis model in vivo were constructed to investigate the effect of TUB-II on tumor growth and lung metastasis. Results TUB-II significantly inhibited the proliferation and metastasis of colorectal cancer both in vitro and in vivo (P < 0.05, 0.01, 0.001). TUB-II significantly upregulated the expression of LLGL2 (P < 0.05, 0.01, 0.001) and inhibited the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway (P < 0.05, 0.01, 0.001), thereby suppressing tumor cell proliferation and metastasis. At the same time, TUB-II inhibited the interaction between murine double minute 2 (MDM2) and LLGL2 to suppress the ubiquitination of LLGL2, thereby stabilizing its expression and exerting an anti-colorectal cancer effect. Conclusion TUB-II inhibits the occurrence and development of colorectal cancer, and its mechanism may be related to the inhibition of LLGL2 ubiquitination and PI3K/Akt signaling pathway.

tubeimoside II  /  lethal (2) giant larvae homolog 2  /  murine double minute 2  /  ubiquitination  /  colorectal cancer