The Effect Of Osteopontin On Enhancing The Invasion Ability Of Liver Cancer Cells And Its Possible Mechanisms

BackgroundAs one of the common malignant tumours, Hepatocellular carcinoma(HCC) threatenspeople with a high level of invasiveness, frequent intrahepatic spread, extrahepaticmetastasis and high mortality. With the development of comprehensive therapy, the highrecurrence rate and poor prognosis of HCC have still not been improved a lot.Here wewant to stop HCC from happening and developing by cutting off its invasiveness andmetastasis. Then OPN (Osteopontin) comes.However, OPN is closely associated withinvasion, metastasis and prognosis of many kinds of tumors, the mechanism is unkonwn.ObjectiveTo investigate the effect of OPN on the invasion of hepatocellular carcinoma cells andthe mechanism by targeting siRNA of OPN.MethodsFirst, we measured the expression of OPN in three HCC cell lines （HepG2,SMMC-7721and MHCC97H）and normal human liver cell line (HL-7702cells) byRT-PCR and Western-blot. Then we detect the invaded ability of these cells to observe therelationship between the expression of OPN and their invaded ability. Second, we down-regulate OPN with siRNA in HepG2and MHCC97H cell lines and determine theexpression of OPN by RT-PCR and Western-blot. Then we measure its effect oninvasiveness of HCC cell lines by transwell and the expression of MMP-2and VEGF byWestern-blot and ELISA.Results1.We find the order of invasive ability of these cells is that MHCC97H＞SMMC-7721＞HepG2>>HL-7702. The expression of OPN in HCC cell lines is higherthan normal human liver cell line HL-7702, and the expression of OPN enhances with theincrease of invasive ability of HCC cell lines（P<0.05).2. Effectively downregulation of OPN by siRNA in HepG2and MHCC97H cell linescan reduce their invasive ability (P<0.05).3. Effectively downregulation of OPN by siRNA in HepG2and MHCC97H cell linescan also reduce the expression of MMP-2and VEGF (P<0.05).ConclusionOPN plays an important role in the invasion of HCC cells, which may be throughregulating MMP-2and VEGF. OPN could be used as a new target in therapy of HCC.