Sirolimus inhibits growth of human hepatoma cells alone or combined with tacrolimus, while tacrolimus promotes cell growth

Figure 1 Proliferation assays showing cell numbers from mean counts of three experiments. Cells were treated as described in Materials and Methods with sirolimus, tacrolimus, or the combination of both. Sir = sirolimus; Tac = tacrolimus. Data are expressed as mean±SE. (A: SK-Hep 1: ^aP = 0.0105; ^bP = 0.0156; ^cP = 0.254; ^dP<0.0001; B: Hep 3B: ^eP<0.0001; ^fP = 0.0654; ^gP = 0.0002; ^hP<0.0001).

Figure 2 Cell-cycle analysis of both cell lines after treatment for 24 h with sirolimus, tacrolimus, or the combination of both at a dose of 25 ng/mL each compound. M1 = Sub-G1 region, indicating cells with small DNA fragments, a typical feature of apoptosis; M2 = G1-Phase; M3 = S-Phase; M4 = G2/M-Phase. The different cell cycle phases (M1-M4) were set in a reference analysis and kept constant throughout the measurements.

Figure 3 Western blot analysis of p53 and bcl-2. SK-Hep 1 cells express wild-type p53. Hep 3B cells harbor a deletion of the p53 gene and express no p53 protein. Expression levels were analyzed by densitometry referring to levels of actin. Relative values to controls are shown.