Inhibitory effects of thymoquinone on human pancreatic carcinoma orthotopically implanted in nude mice

Abstract

To explore the anti-neoplastic and anti-metastatic effects of thymoquinone on the model of human pancreatic carcinoma established by surgical orthotopic implantation (SOI) in nude mice. After a 3-week implantation, 40 mice were randomized into 4 groups: control group, feed with 1% ethanol; low-dose thymoquinone group (L-TQ 5 mg/kg BW daily by i.g.), high-dose thymoquinone group (H-TQ 20 mg/kg BW daily by i.g.) and gemcitabine group (GEM 100 mg/kg BW twice a week by i.p.) (n = 10 each). All treatment sessions lasted for 2 weeks. At Week 8 post-implantation, tumor weight, inhibition rate and the presence of metastasis were evaluated respectively after sacrificing. Immunohistochemistry was used to detect the positive expressions of Ki-67, XIAP (X-linked inhibitor of apoptosis protein) and MMP-9 (matrix metalloproteinase 9) in tumors. The tumor growth-inhibiting rates of L-TQ group, H-TQ group and GEM group were 42.57%, 64.11% and 54.77% respectively. The rates of metastasis in L-TQ group and H-TQ group were 60% and 50% versus GEM group (100%). And the differences had statistical significance (P < 0.05). The positive rates of Ki-67 in group L-TQ and group H-TQ were 37% ± 3% and 32% ± 2% versus group GEM (55% ± 4%). And the differences had statistical significance (P < 0.05). The positive rates of XIAP in group L-TQ and group H-TQ were 30% ± 3% and 28% ± 5% versus group GEM (56% ± 4%). And the differences had statistical significance (P < 0.05). The positive rates of MMP-9 in group L-TQ and group H-TQ were 57% ± 7% and 53% ± 2% versus group GEM (73% ± 4%). And the differences had statistical significance (P < 0.05). Thymoquinone has the anti-neoplastic and anti-metastatic effects on the human pancreatic carcinoma in nude mice. And the above effects may be correlated with the down-regulated expressions of XIAP and MMP-9.