Abstract
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.