To explore the molecular mechanism of γ-aminobutyric acid (GABA) inhibiting the growth of cholangiocarcinoma via cAMP/PKA signal pathway. Methods: QBC939 cells were cultured in different groups and treated with GABA, GABA + 8Br (cAMP agonists), GABA + H89 (PKA antagonist) for 48 hours. MTT assay was used to determine the proliferation of QBC939 cells. Annexin V-FITC/PI binding assay was used to detect apoptosis in the QBC939 cells. Western blot was applied to detect the expression of PKAI and

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... AII and ERK proteins in different groups of QBC939 cells. Animal models of cholangiocarcinoma bearing nude mice were established by subcutane-ous injection of QBC939 cells and randomized into 2 groups: control and GABA-treated groups. The effect of GABA was evaluated after 5 weeks, including tumor volume. The expression of PKAI and PKAII and ERK was detected by Western blot in xenograft tumors. Results: MTT and FCM assays all showed that the inhibitory effect of GABA on the proliferation and the induced apoptosis of QBC939 cells could be antagonized by H89, but not 8Br. Western blot analysis showed that GABA significantly down-regulated the expression of PAK I protein (0.0878±0.003 vs. 0.1521±0.003, t=29.687, P<0.05), up-regulated the expression of PKA II (0.2042±0.012 vs. 0.1461±0.072, t=8.152, P<0.05), and also decreased the expression of ERK protein (0.3683±0.007 vs. 0.4687±0.01, t=13.647, P<0.05) and xenograft tumor volume [(0.50±0.02 vs. 0.32±0.03) cm 3 , t=15.354, P<0.05]. The expression of PKAI and ERK was significantly decreased, and PKAII was increased in GABA-treated group as compared with control group. Conclusions: GABA may inhibit the growth of cholangiocarcinoma cells QBC939 through cAMP/PKA signal pathway, which down-regulated PAK I and up-regulated PKAII expression, and then decreased the expression of ERK.