Thioridazine reverses trastuzumab resistance in gastric cancer by inhibiting S-phase kinase associated protein 2-mediated aerobic glycolysis

Figure 4 Thioridazine combined with lapatinib decreases S-phase kinase associated protein 2/p-protein kinase B/p-mammalian target of rapamycin/glucose transporter type 1 protein levels and glycolysis in gastric cancer cells. A-C: HGC27, HGC27-R and SGC7901-R cells were treated with thioridazine (5 μM) alone or in combination with lapatinib (5 μM) for 24 h. S-phase kinase associated protein 2 (Skp2), p-protein kinase B (Akt), Akt, p-mammalian target of rapamycin, and glucose transporter type 1 protein levels were analyzed by western blotting; D-G: HGC27-R cells were treated with thioridazine (5 μM) and lapatinib (5 μM) alone or in combination for 24 h. The glucose uptake rate and lactate production rate were measured following the manufacturer's instructions; H and I: HGC27-R cells were divided into two groups that were transfected with small interfering RNA (siRNA) negative control or siRNA SKP2 2 for 48 h. Each group was treated without or with thioridazine (5 μM) for another 24 h. The glucose uptake rate and lactate production rate in all groups were measured. ^aP < 0.05; ^bP < 0.01; ^cP < 0.001; ^dP < 0.0001. Thior: Thioridazine; Lap: Lapatinib.