Celastrol inhibits colon cancer cell proliferation by downregulating miR-21 and PI3K/AKT/GSK-3ß pathway.

Celastrol is a traditional Chinese medicine, that is derived from Tripterygium wilfordii. It has been proposed to offer anti-tumor potential. MicroRNAs also play important roles in tumorigenesis. However, the anti-tumor mechanism of Celastrol and whether miRNAs are involved in the process are still unknown. In the present study, MTT assay was used to test the IC50 of Celastrol and cell viability. PCNA, PI3K, Akt, GSK3ß, phosphorylated Akt and GSK3ß were measured by western blotting. Flow cytometry was introduced to detect the apoptosis. We found Celastrol inhibited colon cancer cell viability in a dose-dependent manner companied with PCNA downregulation. Apoptosis was induced by Celastrol. After Celastrol treatment, BCL-2 expression decreased while BAX increased and the Caspase-3 activity was induced. Simultaneously, miR-21 expression was reduced in Celastrol-treated colon cancer cells. miR-21 mimic overexpression could enhance the cell viability, inhibit the apoptosis, decrease BCL-2 expression, increase BAX and induce Caspase-3 activity to some extent which were reversed by Celastrol. In addition, the PI3K/AKT/GSK-3ß pathway was activated by miR-21 mimic but partially arrested by extra-adding Celastrol. Thus, Celastrol may inhibit colon cancer cell proliferation by negatively regulating miR-21 and the PI3K/AKT/GSK-3ß pathway.