Arsenic Trioxide Combined With Celecoxib Hcclm <sub> 3 </ Sub> Hepatocellular Carcinoma After Resection Of Recurrence, Metastasis,

Objective:Discuss the influence of As₂O₃ and Celecoxib on HCCLM₃ hepatoma cell growth,adhesion,movement,invasion and expression of relative gene with hepatoma recurrence and metastasis.Methods:Detect the effect of As₂O₃ and Celecoxib on HCCLM₃ hepatoma cell growth and adhesion with MTT;find out the influence of As₂O₃ and Celecoxib on HCCLM₃ hepatoma cell movement and invasion with Transwell chamber;study the effect of As₂O₃ and Celecoxib on HCCLM₃ hepatoma cell expression of MMP-2, VEGF, CD44V6 and E-cadherin with cell immunohistochemistry.Reaults: As₂O₃ and Celecoxib can inhibit HCCLM₃ hepatoma cell growth and adhesion by time and dose dependent,two drugs have synergetic effect at lower dose level.4.0μmol/l As₂O₃,80μmol/l Celecoxib can inhabit HCCLM₃ hepatoma cell adhesion, movement and invasion after 48 hours disposal,the strength of effect:the group of combination>the group of As₂O₃>the group of Celecoxib>the group of control;4.0μmol/l As₂O₃,80μmol/l Celecoxib can down-regulation expression of MMP-2 alone or allied after 48 hours disposal, but As₂O₃ has the major effect.4.0μmol/l As₂O₃,80μmol/l Celecoxib can down-regulation expression of VEGF after 48 hours disposal,but the group of combination has the most effect,the group of As₂O₃ has similar effect with the group of Celecoxib;4.0μmol/l As₂O₃,80μmol/l Celecoxib can downregulation expression of CD44V6,up-regulation expression of E-cadherin alone or allied after 48 hours disposal,the strength of effect:the group of combination>the group of Celecoxib>the group of As₂O₃>the group of control.Conclusion:As₂O₃ and Celecoxib can inhibit HCCLM₃ hepatoma cell growth, adhesion, movement and invasion,mechanism of action may be achieved by regulation the expression of tumor recurrence and metastasis relative genes,As₂O₃ has the synergetic effect with Celecoxib. Objective:Discuss the influence of As₂O₃ and Celecoxib on tumor recurrence and metastasis after resection of nude mice HCCLM₃ hepatoma.To study the effect of As₂O₃ and Celecoxib on the expression of hepatoma recurrence and metastasis relative genes.Methods:Set up nude mice model of indirect orthotopic implantation of HCCLM₃ hepatoma tissue and patient-like resection model of implanted HCCLM3 hepatoma.Treat nude mice with Celecoxib and As₂O₃;observe the nude mice's general state;sacrifice nude mice after 33 days;measure the volume and quantities of recurrence HCCLM₃ hepatoma;count the quantities of tiny lung metastasis;examine the function of liver and kidney of nude mice;study the effect of As₂O₃ and Celecoxib on the recurrence HCCLM₃ hepatoma tissue's expression of MMP-2,VEGF,CD44V6 and E-cadherin with immuno-histochemistry; measure the expression of VEGF by RT-PCR.Reaults:The condition of recurrence HCCLM₃ hepatoma:the group of control(6/6),the group of Celecoxib(8/8),the group of As₂O₃(5/8),the group of combination(3/8).The volune of recurrence HCCLM₃ hepatoma(mm³): the group of control (1917.00±647.55),the group of Celecoxib(387.69±202.39),the group of As₂O₃(61.63±107.30),the group of combination(4.69±7.24). The condition of HCCLM₃ hepatoma liver metastasis:the group of control(5/6), the group of Celecoxib(2/8),the group of As₂O₃(1/8), the group of combination(0/8).The condition of HCCLM₃ hepatoma tiny lung metastasis:the group of control (5.50±l.05),the group of Celecoxib(1.63±1.60),the group of As₂O₃ (0.88±1.25), the group of combination(0.25±0.7l).all groups haven't statistics significancein on nude mice's weight,the function of liver and kidney.As₂O₃,Celecoxib can down-regulation expression of MMP-2,VEGF, up-regulation expression of E-cadherin in recurrence HCCLM₃ hepatoma tissue,the group of combination has the most effect,the group of As₂O₃ has similar effect with the group of Celecoxib.As₂O₃, Celecoxib can downregulation expression of CD44V6,the strength of effect:the group of combination>the group of As₂O₃>the group of Celecoxib>the group of control.ConcIusion: As₂O₃, Celecoxib can inhibit the volume and quantities of liver recurrence HCCLM₃ hepatoma,two drugs have the additional effect.As₂O₃, Celecoxib can reduce the quantities of tiny lung metastasis,two drugs have the additional effect.As₂O₃ and Celecoxib haven't obvious influence on nude mice's weight,the function of liver and kidney.The mechanism of prevention nude mice HCCLM₃ hepatoma recurrence and metastasis may be achieved by regulation the expression of tumor recurrence and metastasis relative genes. As₂O₃ has the synergetic effect with Celecoxib. Objective:Discuss the synergetic mechanism of As₂O₃ and Celecoxib. Methods:Measure the effect of As₂O₃ and Celecoxib on HCCLM3 hepatoma cell cycle and Apoptosis by flow cytometry.Study the influence of Celecoxib and As₂O₃ on HCCLM₃ hepatoma cell expression of COX-2 and NF-κBp65 with cell immuno-histochemistry.Study the influence of Celecoxib and As₂O₃ on nude mice recurrence HCCLM3 hepatoma tissue expression of COX-2 and NF-κBp65 with immuno-histochemistry.ReauIts: 4.0μmol/l As₂O₃,80μmol/l Celecoxib can affect HCCLM₃ hepatoma cell cycle,block cell cycle to G₀/G₁ period.As₂O₃ and Celecoxib can increase HCCLM₃ hepatoma cell apoptosis, moreover,the effect of combination group is greater than the effect sum of As₂O₃ and Celecoxib group.Experiment in vitro:4.0μmol/l As₂O₃ can upregulation HCCLM₃ hepatoma cell expression of NF-κBp65 and COX-2; 80μmol/l Celecoxib can down-regulation HCCLM₃ hepatoma cell expression of COX-2,has not influence on expression of NF-κBp65.when combition of two drugs,Celecoxib can decrease HCCLM₃ hepatoma cell expression of COX-2 secondary by activation of NF-κB which had been activated by As₂O₃. Experiment in vivo:As₂O₃ can down-regulation recurrence HCCLM₃ hepatoma tissue's expression of NF-κBp65 and COX-2,Celecoxib can down-regulation recurrence HCCLM₃ hepatoma tissue's expression of COX-2,has not influence on expression of NF-κBp65.when combition of two drugs,As₂O₃ and Celecoxib can decrease obviously recurrence HCCLM₃ hepatoma tissue's expression of COX-2.Conclusion: Celecoxib and As₂O₃ have synergism on increasing of HCCLM₃ cell apoptosis.Celecoxib can inhibit COX-2 expression secondary by activation of NF-κB which had been activated by As₂O₃ in vitro.As₂O₃ has cooperation with Celecoxib on inhibition of COX-2 expression by inactivation of NF-κB in vivo.