| Background and aimHepatocellular carcinoma (HCC) is one of the most common solid tumors throughout the world. Surgical ablation and liver transplantation are the most effective measures for treating HCC, but it is not satisfactory. Metastasis and recurrence of HCC are the maximal barrier influencing therapeutic effect. Chemical therapy is the most important rescue treatment for metastasis and recurrence of HCC. Chemotherapy drugs kill cancer cells mainly through promoting tumor cell apoptosis, which is the purpose of the treatment of HCC. On the one hand, chemotherapy drugs induced tumor cells apoptosis, on the other hand chemotherapy drugs activate a series of biological signals within the tumor cells, which enhance the resistance of tumors to the chemotherapy drugs. All the factors, which restrain or promote tumor cell apoptosis, determine the apoptosis of the tumor cells.As we have know, vascular endothelial growth factor (VEGF) plays a very important role in mediating tumor angiogenesis, associated with tumor progression, invasion, metastasis, and poorer survival of patients with HCC. VEGF is considered to be the main stimulating factor angiogenesis in HCC. Recently, vasohibin-1was identified, and it is a different type of endogenous inhibitor of angiogenesis. Therefore, some researchers pay attention to the vasohibin-1, which participates in the occurrence and development of tumor angiogenesis new disorders.Nuclear factor-KB (nuclear factor-κb, NF-Kb) is a kind of widespread presence of transcription factors, which is closely related to apoptosis, immune response. Recent study found that the NF-κb can be activated by a variety of chemotherapy drugs, especially interference the nucleic acid generated antitumor drugs, and through a variety of mechanisms involved in the formation of drug-resistant tumor cells and is closely related to tumor chemotherapy. Besides, the study found that the NF-κb also has correlation with the apoptosis in embryonic. people gradually realized that the chemotherapy drug resistance of the tumor is closely related to the apoptosis, which regulated by the NF-Kb, NF-Kb in tumor cells may be associated with loss of inhibiting factor expression, structural activation factors leading to excessive activation of NF-Kb. The role of NF-Kb and its application in practice is becoming the focus at present. Activated NF-Kb plays the role of inhibiting tumor cell apoptosis, and the resistance to apoptosis is very various, which has been confirmed in liver cancer, lymphoma, gastric cancer and other tumors.Icariin, as a major extract of epimedium, is a kind of natural compounds, it has anti-tumor and other pharmacologic effect. The ICA, as a kind of common traditional Chinese medicine, has the function of promoting blood circulation and enhancing the immunity and no obvious adverse reaction, and has a wide range of pharmacological effects on the cardiovascular system, cardiovascular system and bone metabolism and the immune system and anti-tumor treatment. It can inhibit the growth of tumor cells and induce the apoptosis of tumor cells. We investigate the expression of NF-Kb and Vasohibin-1in HCC and their roles in the tumorigenesis and development process, at the same time, we investigate the correlation between of them. We study whether ICA can strengthen the antitum or activity of arsenic trioxide in the treatment of HCC, and carry on the beneficial exploration to elucidate the pathogenesis of liver cancer and improve the effect of liver cancer chemotherapy through the experiment.Methods1.The expression of vasohibin-1and NF-Kb in HCC:Formalin-fixed and paraffin-embedded106HCC tissues and corresponding adjacent non-tumorous liver tissue (ANLT) were retrieved from the Department of Pathology, Shandong Provincial Hospital and Jining NO1people’s hospital. The expression of NF-Kb and vasohibin-1in HCC were detected by immunochemistry. We investigate the correlation between the vasohibin-1and NF-kb expressed in the HCC.2. Based on determined by MTT test and flow cytometry instrument to detect cell proliferation and apoptosis, respectively. The changes of the level of ROS and mitochondrial membrane potential were analyzed by the fluorescent signals.The expression of protein immunoblot assay protein, enzyme-linked immunosorbent assay to detect the activity of NF-Kb.Results1.The expression of vasohibin-1in HCC:Cytoplasm high expression of vasohibin-1was detected in68.9%(73/106) of the HCC tissues, which was significantly higher than that in16.04%(17/106) of adjacent non-tumorous liver tissue (ANLT)(P<0.001). According to the results of chi-square analysis, the high expression of Vasohibin-1in HCC is higher than the adjacent to carcinoma non-tumorous liver tissues(χ2=60.55, P<0.001).The expression of NF-κb in HCC:Cytoplasm high expression of NF-Kb was detected in71.70%(76/106) of the HCC tissues, which was significantly higher than that in23.58%(25/106) of adjacent non-tumorous liver tissue (ANLT)(P<0.001). According to the results of chi-square analysis, the high expression of NF-Kb in HCC is higher than the adjacent to carcinoma non-tumorous liver tissues(χ2=49.19, P<0.001).The relationship between the expression level Of Vasohibin-1and NF-Kb:There were19cases which the expression of Vasohibin-1were low positive in76cases of NF-κb high positive expression in HCC tissues, There were16cases which the expression of Vasohibin-1were high positive in30cases of NF-Kb low positive expression in HCC tissues. According to the results of chi-square analysis, the expression of NF-kb has not correlated with the Vasohibin-1in the HCC (χ2=4.70, P>0.05).2. Icariin could inhibit the proliferation of HCC and induce apoptosis in all of the HCC, which depended on the dose of the treatment. Both in vivo and in vitro experiments, Icariin could strengthen the antitumor activity of arsenic trioxide. The antitumor activity and the effect on the strengthening of arsenic trioxide have correlated with the generation of ROS and the activity of NF-Kb in HCC.Conclusion 1. The expression of vasohibin-1protein was high in HCC, and it was low in adjacent non-tumorous liver tissue. Vasohibin-1protein may be used as an important reference value for clinical markers in HCC, which to judge the occurrence, development and prognosis of HCC. The expression of NF-xb protein was high in HCC, and NF-Kb inhibited tumor cell apoptosis, promoted tumor cell proliferation perhaps, but there is no correlation between the expression of NF-Kb protein and vasohibin-1protein in HCC.2. Icariin could strengthen the anti-tumor activity of arsenic trioxide in HCC in our research work. So we think that the combination therapy of Icariin and arsenic trioxide could optimize the treatment of arsenic trioxide in HCC. |
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