ShRNA-mediated silencing of the PI3K p85α gene suppresses colorectal tumor cell migration and invasion

Phosphatidylinositol 3-kinase (PI3K) plays an important role in cell growth, proliferation and motility. The regulatory subunit, p85α, is the most abundantly expressed regulatory isoform of PI3K and is essential for the activation of PI3K. PI3K p85α is often over-expressed in colorectal cancer (CRC) cells, but its role in the migration and invasion of CRC remains unclear. In this study, lentivirus-mediated PI3K p85α-specific shRNA was used to knock down PI3K p85α expression in CRC cells. Cell wound healing and transwell assays were then performed to examine the effect of PI3K p85α on cell migration and invasion, respectively. Furthermore, the expression of cellular proliferation and migration proteins was assessed in PI3K p85α knockdown CRC cells. Finally, in vivo metastasis assays were performed to identify whether the knockdown of PI3K p85α suppressed spleen and liver metastases in nude mice. The results revealed effective inhibition of the migration and invasion of PI3K p85α knockdown CRC cells, partially by regulating cell adhesion and migration-related proteins such as MMP-2, MMP-9 and COX-2. Moreover, knockdown of PI3K p85α significantly suppressed tumor metastasis in nude mice. Our findings show that PI3K p85α plays an important role in the migration and invasion of CRC. More importantly, further investigations suggest that the PI3K pathway may regulate CRC development by modulating cellular proteins related to extracellular matrix formation and cell adhesion. These results improve our understanding of the detailed mechanism of the PI3K pathway in the regulation of tumor metastasis.