Abstract: Objective To investigate the effect of fluoxetine on proliferation and apoptosis of HepG2 cells and its mechanism. Methods We treated HepG2 cells with different concentrations of fluoxetine respectively for 24 hours. Flow cytometry was used to detect cell cycle of HepG2 cells treated with different concentrations of fluoxetine. In HepG2 cells treated with 12.5 μM fluoxetine for 0, 6, 12 and 24 hours, real-time polymerase chain reaction were used to detect the mRNA expressions of Bcl-2 and Bax, and Western bolt was used to detect the protein expressions of Bcl-2, Bax and caspase-3. Results It was showed that the cell percentages in G2/M phase were 9.63% ± 0.33%, 10.12% ± 0.86%, 19.68% ± 4.31% and 22.74% ± 2.46% after HepG2 cells treated with control, 5 μM, 10 μM and 12.5 μM of fluoxetine for 24 hours, respectively. And the cell percentages in G2/M phase in 10 μM and 12.5 μM groups were statistically different from that in control group (both P<0.05). The mRNA levels of Bcl-2 in HepG2 cells were gradually reduced as the time of incubating with 12.5μM fluoxetine increased (0, 6, 12 and 24 hours). The differences were statistically significant between the 0-hour group and other groups, respectively (all P<0.05). While there was no statistical difference in the Bax mRNA levels between control and other groups, respectively (all P>0.05). The protein expression level of Bcl-2 began to decrease after 12-hour incubation while the protein expression level of Bax was not significantly changed. The protein expression levels of Bax/Bcl-2 and caspase-3 began to increase after 12-hour incubation. Conclusion Through influencing HepG2 cell cycle, reducing the expression of anti-apoptotic protein Bcl-2 and activating caspase-3, fluoxetine can inhibit proliferation and induce apoptosis of HepG2 cells.

Key words: HepG2 cell, Fluoxetine, Proliferation, Apoptosis, Mechanism