Dihydrotanshinone I (DHTS), extracted from Salvia miltiorrhiza, has been previously identified as the most effective compound against cancer cells among Salvia miltiorrhiza extracts. However, the therapeutic benefits of DHTS in ovarian cancer and its underlying mechanisms remain unclear. Here, researchers confirmed that DHTS exhibits cytotoxic effects on chemotherapy-sensitive ovarian cancer cells, both alone and in combination with platinum-based chemotherapy. DHTS inhibited the proliferation and migration of ovarian cancer cells in vitro and in vivo by regulating the PI3K/AKT signaling pathway. Combination treatment with DHTS and cisplatin enhanced DNA damage in ovarian cancer cells. In summary, these findings suggest that DHTS induces ovarian cancer cell death by causing DNA damage and inhibits ovarian cancer cell proliferation and migration.
Here, researchers investigated whether DHTS inhibits ovarian cancer cell migration and invasion by regulating PIK3CA transcription. They performed wound healing assays and Transwell chamber assays on wild-type, empty vector-transfected, and PIK3CA-overexpressing (PIK3CA-OX) A2780 cells. In the wound healing assay, the wound closure rate of empty vector-transfected A2780 cells was similar to that of wild-type cells, while PIK3CA-overexpressing A2780 cells showed significantly higher migration ability after 24 hours of DHTS treatment compared to the two control cell lines (Figure 1A, B, upper panel). In the Transwell assay, cells were seeded into the upper chamber of the filter membrane and allowed to migrate for 24 hours in the presence of DHTS. The number of wild-type cancer cells that migrated to the lower side of the filter membrane was similar to that of empty vector-transfected cells. However, compared to the other two cell lines, the migration and invasion ability of PIK3CA-overexpressing A2780 cells was significantly enhanced by 30%-50% (Figure 1A, B, lower panel). These data suggest that PIK3CA is essential in the migration and invasion process of DHTS-treated ovarian cancer cells. On the other hand, DHTS may reduce the migratory ability of ovarian cancer cells by inhibiting the PI3K pathway.
Figure 1. Overexpression of PIK3CA gene increases cell migration and invasion of DHTS-treated A2780 ovarian cancer cells. (Wang X, et al., 2020)