Background and purpose: Tetrandrine is a natural compound whose role in retinoblastoma remains unclear. This study investigated the effects of tetrandrine (Tet) on human retinoblastoma cells. Methods: CCK-8 assays were performed to analyze the effects of Tet on viability of retinoblastoma cells. The apoptosis rate was determined by Annexin V/PI assays. After staining with 2′

7′-dichlorofluorescin diacetate (DCFH-DA)

cellular reactive oxygen species (ROS) was measured by flow cytometry. Akt and p-Akt were detected by Western blot. Results: Tet inhibited cell viability of retinoblastoma cells. After treatment with Tet (4

8

10 and 20 μmol/L) for 24 h

cell viability inhibition rates of WERI-Rb-I were 5.7%

25.0%

55.1% and 84.9%

whereas inhibition rates of Y79 cells were 2.4%

 2.9%

23.8% and 54.2% (P0.01). In cells treated with 10 μmol/L of Tet for 12

24 and 48 h

cell viability inhibition rates of WERI-Rb-I were 6.0%

45.5% and 74.7%

whereas inhibition rates of Y79 cells were 2.9%

19.4% and 43.3% (P0.01). Tet induced retinoblastoma cell apoptosis. After treatment with Tet (10 μmol/L) for 24 and 48 h

apoptosis rates of WERI-Rb-I were (23.70±1.75)% and (34.83±3.15)%

respectively

whereas apoptosis rates of Y79 cells were (9.62±2.69)% and (14.97±1.50)%

respectively (P0.01). Apoptosis inhibitor Z-VAD-FMK attenuated Tet-induced cell death (P0.05). ROS levels were indeed increased in cells treated with Tet (10 μmol/L) for 6 and 12 h (P0.01)

while N-Acetyl-L-cysteine (NAC) decreased Tet-induced ROS (P0.01). After ROS was inhibited by NAC

apoptosis rate was decreased compared with the control (P0.01). Further study indicated that Tet inhibited PI3K/Akt pathway in retinoblastoma cells. Conclusion: Tet induces cell apoptosis via increasing ROS synthesis and inhibiting PI3K/Akt pathway.