Gambogic acid regulates the migration and invasion of colorectal cancer via microRNA-21-mediated activation of phosphatase and tensin homolog

Gambogic acid (GA) has been reported to inhibit cancer cell proliferation and migration and enhance apoptosis. Several signaling pathways were identified to be involved in GA function, including PI3K/Akt, caspase-3 apoptosis and TNF-α/NF-κB. However, to the best of our knowledge, the association between miRNA and GA has not been explored. The present study initially demonstrated that GA could inhibit HT-29 cancer cell proliferation using an MTT assay. In addition, a Transwell assay and a wound-healing assay respectively indicated that GA inhibited HT-29 cancer cell invasion and migration, which was also confirmed by the increased MMP-9 protein expression. Furthermore, GA induced the apoptosis of HT-29 cancer cells in an Annexin V and PI double staining assay. Moreover, treatment with GA significantly decreased miR-21 expression in these cells. Additionally, western blot analysis demonstrated that GA treatment enhanced the activation of phosphatase and tensin homolog (PTEN) along with the suppression of PI3K and p-Akt. Furthermore, miR-21 mimics reversed all the aforementioned activities of GA, which indicated that miR-21 was the effector of GA and blocked PI3K/Akt signaling pathway via enhancing PTEN activity. In summary, GA induced HT-29 cancer cell apoptosis via decreasing miR-21 expression and blocking PI3K/Akt, which may be a useful novel insight for future CRC treatment.