E.coli43013in Combination With Sorafenib For Hepatocellular Carcinoma: An Experimental Research

ObjectiveThe comparative Study of the therapeutic effect and potential mechanismof Simple application E.coli, simple application Sorafenib, E.coli in combinationwith Sorafenib for hepatocellular Carcinoma of SD rats transplantedWalker₂56cells line.MethodsSD rats of Walker₂56hepatocellular carcinoma model were establishedafter the following step.Step1: Culturing Walker₂56cell line and injecting Walker₂56cell intothe right subcutaneous armpit of Wistar rats’ forelimb.Step2: The subcutaneous tumor of Wistar rats, when its diameter reaches2cm, was taken out and put into the normal saline （0-5℃） and incised into0.1-0.2cm pieces.Step3: The well-prepared tumor pieces were implanted into the SD rat’sleft anterior lobe of liver under sterile conditions.Step4: After11days, the Transplanted-tumor SD rats’stomach wasincised, and the tumor was exposured and measured. The SD rats, whosetumor diameter scope is between0.5-1.0cm and those are no ascitic fluid, wasselected into the experimental study of E.coli in combination with Sorafenib. And twenty eight liver transplanted-tumour SD rats, whose tumor diameterscope is between0.5-1.0cm and those are no ascitic fluid,were divided into fivegroups after11days.1.Negative Control group [G（A）,n=5]；2. Positive Controlgroup [G（B）,n=5]；3. E.coli group [G（C）,n=5]；4. Sorafenib group[G（D）,n=5]；5. E.coli in combination with Sorafenib group [G（E）,n=5]. Thebody weight of rats were measured at3,6,9,12,15,18,20days after treatment.The tumor volume and relative tumor volume were calculated by data measuredat20days after treatment.All the rats were sacrificed and pathologic change,immunohistochemistry and blood bacterial culture were performed after20days.ResultsSD rats of Walker₂56hepatocellular carcinoma model were successfullyestablished to one hundred percent. And only32.2%SD rats, whose tumordiameter scope is between0.5-1.0cm and those are no ascitic fluid, was selectedinto experimental study. The growth of tumors in the animal models wasincrease rapidly after implantation and difference between individuals, and someof them have ascitic fluid.Analyzing from the result of HE,We know that Tumor growth inhibition inE.coli group and Sorafenib group and Combination group were66.7%and80%and100%respectively. Analyzing from the result of IHC, E.coli candestroy metalloproteinases9and vimentin,that play an important role in tumorcells invasion function, and has the function of inhibiting tumor cellproliferation.What’s more,there are no bacteria in each group.Conclusions1. SD rats of Walker₂56hepatocellular carcinoma model is a kind ofstable and efficient tumor model. 2. E. coli can selectively inhibit the proliferation of tumor cells, can destroymetalloproteinases9and vimentin,that play an important role in tumor cellsinvasion function,and no damage to normal cells and tissues. Intratumorinjection of E.coli has soluble tumor effect, and is a safe and effective antitumormethod.3. E.coli in combination with Sorafenib has the function of synergisticanticancer effect.