Abstract
Objective To investigate the inhibitory effect and mechanism of arsenic trioxide on hepatocellular carcinoma (HCC) cells migration induced by low dose of sorafenib. Methods Human HCC cells MHCC97H in logarithmic phase were treated with 2 μmol/L arsenic trioxide (arsenic trioxide group), 3 μmol/L sorafenib (sorafenib group), 2 μmol/L arsenic trioxide + 3 μmol/L sorafenib (combination group), 50 μmol/L LY294002(LY group) and 3 μmol/L sorafenib + 50 μmol/L LY294002 (LY+ sorafenib group) respectively. Dimethyl sulfoxide (DMSO) was used in the control group. Wound healing assay and Transwell migration assay were used to detect the ability of horizontal and vertical cell migration. The expression of p-Akt, E-cadherin, Vimentin and Snail proteins was measured by Western blot. The experiment data were compared using one-way ANOVA and Bonferroni test. Results Wound healing assay revealed that the horizontal migration speed in the sorafenib, arsenic trioxide and combination groups was (1.59±0.14), (0.39±0.08) and (0.58±0.12) times of that in the control group (t=7.20, -12.58, -6.62; P<0.05). Transwell migration assay revealed that the number of cells in the sorafenib, arsenic trioxide, combination and control groups was 285±26, 169±18, 194±19 and 228±9 respectively. Compared with the control group, the number of cells was significantly increased in the sorafenib group (t=3.48, P<0.05), whereas significantly decreased in the arsenic trioxide group (t=-3.80, P<0.05). The number of cells in the combination group was significantly decreased than that in the sorafenib group (t=-5.67, P<0.05). Western blot revealed that the expression of p-Akt, Snail and Vimentin proteins was up-regulated, whereas the expression of E-cadherin protein was down-regulated in the sorafenib group compared with those in the control group. Compared with the control group, the expression of p-Akt, Snail and Vimentin proteins was down-regulated whereas the expression of E-cadherin protein was up-regulated in the arsenic trioxide, combination, LY and LY + sorafenib groups. Conclusion Arsenic trioxide can inhibit the epithelial-mesenchymal transition and reverse the promoting effect of low-dose sorafenib upon MHCC97H cell migration through suppressing the activation of PI3K/Akt/Snail signaling pathway. Key words: Carcinoma, hepatocellular; Sorafenib; Arsenic trioxide; Epithelial mesenchymal transition
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