Combined antitumor effects of 1,25‑dihydroxy vitamin�D3 and Notch inhibitor in liver cancer

The combined antitumor effects of 1,25‑dihydroxy vitamin D3 [1,25(OH)2D3] and the Notch inhibitor N‑[N‑-(3,5‑difluorophenacetyl)‑L‑alanyl]‑S‑phenylglycine t‑butyl ester (DAPT, a synthetic γ secretase inhibitor) in liver cancer cells remain to be fully elucidated. In the present study, HepG2 cells were divided into six groups and different treatments were applied: Control, 10‑10 M 1,25(OH)2D3, 10‑8 M 1,25(OH)2D3, 10‑6 M 1,25(OH)2D3, 1 µM DAPT, 5 µM DAPT, 10 µM DAPT, and 10‑6 M 1,25(OH)2D3 + 10 µM DAPT. The proliferation, cell cycle, apoptosis, migration and invasion of the cells were then examined. The expression levels of Notch and its ligand Jagged were detected by reverse transcription‑quantitative polymerase chain reaction and western blot analyses. The results revealed that 1,25(OH)2D3 inhibited cell proliferation, migration and invasion; arrested cell cycle at the G1 phase, and promoted apoptosis in a concentration‑dependent manner between 10‑10 and 10‑6 M. DAPT inhibited cell proliferation, migration and invasion, arrested cell cycle at the G1 phase, and promoted apoptosis in a concentration‑dependent manner between 1 and 10 µM. Additionally, 1,25(OH)2D3 and/or DAPT reduced the expression of Notch1, Notch2, Jagged1 and Jagged2. The co‑application of 10 µM DAPT further increased the anticancer effect of 10‑6 M 1,25(OH)2D3. Collectively, these results indicated that the treatment of HepG2 cells with 1,25(OH)2D3 inactivated Notch signaling, prevented proliferation, migration and invasion, and promoted apoptosis. The combined application of 1,25(OH)2D3 with DAPT may be a useful treatment for preventing the onset or progression of liver cancer.