Objective To research the effect of GBC-SD on proliferation, apoptosis, expression of CD147 and activity of matrix metalloproteinase (MMP)-9 in gallbladder carcinoma cells, with single and combination therapy of CD147 antagonist peptide and doxycycline. Methods Gallbladder carcinoma cells were treated with antagonist peptide (AP-9) (50, 100, 200, 400 μg/ml) or DOX (5, 10, 20, 40 μg/ml) alone and combination therapy (AP-9 200 μg/ml + DOX 20 μg/ml) for 12, 24 and 48 h, then the inhibition rate of proliferation was detected by cell counting kit-8 (CCK-8), expression of CD147 was detected by Western blotting, the activity of MMP-9 was detected by gelatin zymography, and the early apoptosis rate was detected by flow cytometry with Annexin V/propidium iodide (PI) staining. Results After treatment with several concentrations of AP-9, the apoptosis rate [(2.13±0.10)% and (2.92±0.19)%] was higher (P=0.002, P=0.001) than control group [(1.58±0.08)%]; the activity of MMP-9 [(320.08±33.90), (249.59±33.63), (259.63±34.08) and (172.31±35.20)] was reduced (P=0.013, 0.002, 0.003 and 0.001 respectively) as compared with that in control group; and cell proliferation was inhibited as compared with that in control group (P=0.001). After treatment with several concentrations of doxycycline, the apoptosis rate [(3.25±0.12)% and (3.63±0.24)%] was higher (P=0.001) than in the control group [(1.58±0.08)%]; the activity of MMP-9 [(203.52±18.25), (175.22±23.30), (147.86±22.83) and (109.99±29.22)] was reduced (P=0.001) as compared with control group [(446.08±42.42)]; cell proliferation was inhibited as compared with control group (P=0.001); the expression level of CD147 [(0.97±0.12), (0.80±0.10), (0.69±0.11) and (0.51±0.12)] was reduced (P=0.001) as compared with cotrol group [(2.04±0.15)]. As compared with treatment alone, cell proliferation [(38.78±0.39)%, (43.76±0.71)% and (52.00±0.91)%] was increased (P=0.001, P=0.003), the activity of MMP-9 [(110.19±24.74)] was reduced (P=0.001, P=0.024), and the apoptosis rate [(3.73±0.29)%] was elevated after combination therapy (P=0.001, P=0.048). Conclusion DOX can down-regulate the expression of CD147. AP-9 and DOX alone or in combination can inhibit the proliferation of gallbladder cancer cells, inhibit the activity of MMP-9, and promote apoptosis, and the inhibitory effect was enhanced after combination therapy. Key words: Gallbladder carcinoma; CD147; Extracellular matrix metalloproteinase-9; Antagonist peptide; Doxycycline