Akt downregulation is involved in cannabinoid antitumoral action. (A and B) Viability of N202.1A cells in response to (A) increasing concentrations of THC or JWH-133 or (B) 6 μM THC or 10 μM JWH-133 with or without 2 μM SR141716 (SR1) and/or SR144528 (SR2) for 48 h. Data are expressed as % of vehicle-treated cells, set at 100%. (C) Growth of N202.1A-derived xenografts treated with THC (left panel) or JWH-133 (right panel) with or without SR2. (D) Phospho-Akt and phospho-S6 ribosomal protein (p-S6) levels in N202.1A cells challenged with THC, as determined by Western blot. Total Akt and α-tubulin levels were used for normalization. (E) Phospho-Akt and total Akt levels in N202.1A cells retrovirally transduced with myristoylated Akt (pBABE-Myr-Akt) or the corresponding empty vector (pBABE). (F) Cell viability of pBABE- or myr-Akt-transduced N202.1A cells in response to THC exposure for 72 h. (G and H) Time course of the volume of pBABE-N202.1A-derived (left panels) and myr-Akt-N202.1A-derived (right panels) tumors treated with THC (G), JWH-133 (H) or the corresponding vehicle. *, p < 0.05; **, p < 0.01 vs vehicle-treated cells or tumors; #, p < 0.05; ##, p < 0.01 vs cannabinoid alone-treated cells (B) or vs THC-treated pBABE-transduced cells (F).