| Primary hepatocellular carcinoma (HCC) is well-known as the most common and aggressive malignancy worldwide. At present, it has been ranked as third leading cause of cancer-related death worldwide, as well as the second or third leading cause of death due to cancer in our country both in the female group and male group. Some sufferer has been diagnosed only after the surgical curative treatment couldn't be operated, who has been suffered widely metastasis. Despite tremendous achievements being made basically and clinically especially in the surgical resection during the past decades, the prognosis of HCC remains dismal, ever the 5-years recurrence and the metastasis rate after the curative resection was still more than 6o percent to 8o percent, the high recurrence rate becomes the major obstacle of improving prognosis. For those Patients who have advanced stage disease, Poor liver function, or recurrent tumors after local treatments, It has been attested in lots of experiment that HCC is suppressed by the component of this compound. It has shown remarkable curative effect inducing tumor cell apoptosis in HCC. But the curative effect, treatment of the clinic tumor, is very disappointed. Nuclear factor Kappa B is widely distributed in eukaryotic cells. In recent years, NF-κB has become hotspot of studying. It has been reported that NF-κB plays a Key role in cell proliferation, apoptosis, invasiveness, metastasis, tumorigenesis, and angiogenesis. Recently, it has been reported that the resistance of tumor chemotherapy is related with NF-κB. Systemic Pharmacologic treatment is the final and main therapy; unfortunately the response rate to traditional chemotherapy for HCC patients is quite low and the outcome is also poor, ever to show low curative effect, which is believe as 10 percent to 20 percent. Hence, new drugs with a higher effect and hypotonic or chemotherapy method which combined traditional and new drugs are urgently needed Key. This study is designed for the NF-κB signal pathway inhibitor PDTC to take action in vivo to confirm that they have synergistic effect for inhibition of HCC. It also can supply evidence for clinic study.[Object]Take human hepatocellular carcinoma cell(HCC) as the research object, to investigate the effect and possible synergistic mechanism of pyrrolidine dithiocarbamate(PDTC) on inhibition effect of NF-κB pathway and tumor recurrence after resection of hepatocellular carcinoma in nude mice and liver metastasis, lung metastasis and its associated molecular mechanisms.[Method]1) To construct a simulation of human hepatocellular carcinoma recurrence after resection of the tumor with high metastatic nude mice model, to divide these nude mice into 2 group by measure the bulk of the primary focus including control group; PDTC group; to observe the tumor recurrence and intrahepatic metastasis, lung metastasis2) To assay by immunohistochemistry the protein expression of tumor recurrence after surgical curative resection including VEGF, MMP-2, TIMP-2, and E-Cadherin.3) Statistical analysis:All data were analyzed by SPSS13.0 statistical software. Data were expressed as mean±S.D. Two independent samples were analyzed by T-test. The others data were analyzed by one-way ANOVA followed by LSD multiple comparison tests. Rank data were analy2ed by 2 Independent Samples Test. P-values were considered to be significant at<0.05. [Result]In our vivo animal investigation, control group result as the rate of positive intrahepatic recurrence is 100%, the bulk of the tumor is 1153±28mm3,the of PDTC-treated group is 100%, and the bulk of tumor is 863±14mm3,there is obviously variation in the tumor recurrence between the two group in general speaking, P=0.0045, The intrahepatic metastasis:the amount in control group is 4.1±0.1,the segment involve is 3.1±0.2, P=0.043, compared with control group, the PDTC-treated group result as 2.9±0.2, 2.0±0.3, There is obviously variation in the intrahepatic metastasis, The lung metastasis:the rates of positive lung metastasis in both group is 100%, the number of metastasis in control group is 7.1±0.1, and the number of metastasis in PDTC-treated group is 5.7±0.3, the number of distant organ metastasis is 3.2±0.3 in control group, and the number of distant organ metastasis is 1.9±0.3, P=0.00001, the immunohistochemistry results showed:compared with the control group, The protein expression of tumor recurrence after surgical curative resection including VEGF, MMP-2, and E-Cadherin has obvious variation compared with the control group in PDTC-treated group except TIMP-2. Control group:VEGF 68.60±7.36, MMP-2 75.56±4.18, TIMP-2 27.19±2.76, E-Cadherin 20.37±4.13, the PDTC-treated:VEGF 54.35±4.26, MMP-2 65.80±5.58, TIMP-2 27.19±2.76, E-Cadherin 23.14±2.17The differences compared with control group were obviously statistical significant.[Conclusion]The construction of tumor recurrence and metastasis after surgical resection of hepatocellular carcinoma in nude mice model increasingly play their important role in drug treatment research for recurrence and metastasis after liver cancer surgery, in this investigation, there is obviously significant inhibition that PDTC treat the hepatoma cells in vivo by normal administration of drugs. Suppression of recurrence and metastasis in distance were obviously evident, the primary hypothesis may be that the active ingredient in vivo attribute to the function of metabolism reduced in efficacy. Advantage relevant experiments will be confirmed.
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