Morphology and mechanism of vasculogenic mimicry in colon carcinoma
AIM: To explore whether vasculogenic mimicry (VM) exists in colon carcinoma and the possible mechanism. METHODS: Three-dimensional culture system of human colon carcinoma cell line SW480 was constructed to observe VM under inverted microscope, and the ultrastructure of VM was observed under trans-electron microscope. The proliferation inhibitory rates of SW480 cells induced by the specific inhibitor 2-(4-morpholinyl)-8-phenyl -4H-l-benzopyran-4-one (LY294002) of the signaling pathway phosphatidylinositol-3 kinase(PI-3K) were detected by Methyl thiazolyl tetrazolium(MTT) method. After SW480 cells were treated with LY294002 10 μmol/L for 72 h, the density of VM was observed under light microscope. Moreover, the expressions of osteopontin ( opn ), matrix metalloproteinase2 ( romp2 ) genes were assessed by reverse transcription-polymerase chain reaction(RT-PCR). After SW480 cells were treated with LY294002 10 μmol/L for 24-72 h, the expressions of protein kinase B (PKB), phospho-protein kinase B (p-PKB) proteins were analyzed by Western Blot. RESULTS: During Three-dimensional culture, SW480 cells can form VM. The result of trans-electron microscope validated the presence of VM. After LY294002 treatment, the growth of SW480 cells was inhibited significantly in a time and dose dependent manner, and the inhibition rates were 13.01% - 67.55% (P <0.01 ). When treated for 72 h ,The density of VM was decreased from[ ( 12.50 ± 3.27 ) to (2.60 ± 1.07) , P <0.01 ], the expressions of opn, mmp2 genes were lower in LY29400210 10mol/L groups than in control groups [ ( 0. 31 ± 0. 01 ) vs (0.75 ±0.03),(0.20 ±0.04) vs (0.55 ±0.05), P <0.01]. The expression of p-PKB protein was down-regulated( P < 0. 01 ) , but it had no change on PKB. CONCLUSION: IN294002 can inhibit the formation of VM in colon carcinoma by reducing opn and romp2 expression, which might be related to the inhibition of PI3K/PKB signaling pathway.
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