| Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, and its mortality is3rd among all of the tumors, just after the lung cancer and gastric cancer. Hepatocellular carcinoma has a higher morbidity in Asian countries due to the high incidence of HBV infected. At the same time, HCC’s happen is also increasing in Western countries as the growing rates of HCV infected. Surgical resection is the best method in treating with HCC, improving the quality of the life as well as lengthening the duration of life. But, unfortunately, mgst of the patients are at the later period of the disease, making them ineligible for surgical resection. Only30%to40%of the patients are eligible for surgical management involving hepatic resection. Even after surgical resection, the prognosis remains unsatisfactory due to a high incidence of postoperative recurrence. Liver transplantation is another potential curative treatment for early HCC, but its application is limited by the shortage of liver grafts. There is lack of clinical efficacy with existing systemic chemotherapies in unresectable HCC patients with macrovascular invasion or extrahepatic metastasis, and the prognosis is poor. Hepatocellular carcinoma is biologically heterogeneous, dysregulation of apoptosis signaling pathway contributes to the proliferation and metastasis of HCC. Activation of apoptosis pathways eventually result in activation of caspases, a key mechanism by which cytotoxic drugs kill tumor cells.Somatostatin (SS) is a cyclic polypeptide hormone, it and its analogues with a wide range of in vivo antitumor effect. Octreotide (OCT) is a synthetic somatostain octapeptide analogues. Recent studies confirm that OCT can inhibit the growth of a variety of tumors such as colon, pancreatic, etc. In this study, We take human hepatoma cell Huh-7as a model to detect different concentrations of octreotide on the proliferation of Huh-7cells, cell cycle and apoptosis in vitro by MTT and flow cytometry analysis techeniques, and further by Western blot protein detection technology to analyze the mechanism. In vivo, we choose nude as the tumor-bearing carrier, observe the impact of octreotide on the growth of Huh-7cell transplanted tumor, and give evaluation of blood vessel formation of transplanted tumors.ObjectiveIn vitro,to investigate the effects and its mechanism of octreotide on the proliferation, cell cycle and apoptosis of human liver cancer Huh-7cells.In vivo, to observe the influence of octreotide on tumor growth in tumor-bearing nude mice.MethodsIn vitro, after treatment with various concentrations of octreotide, the proliferation of Huh-7cells was measured by MTT assay, cell cycle and apoptosis were detected by flow cytometry, and Caspse-3was detected by western blot way.In vivo, nude mice implanted with Huh-7cells were given octreotide for4weeks, and tumor growth were evaluated.Tumor microvessel density was investigated using immunohistochemical technology.ResultsThe proliferation of Huh-7cells was significantly inhibited by octreotide treatment. The growth inhibition rates were68.83%and80.33%with10-5mol/L octreotide treatment for24and36h, respectively. In addition, octreotide is able to effectively induce G1phase arrest and apoptosis of Huh-7cells. After24h treatment with10-5mol/L octreotide, the apoptotic Huh-7cells reached55.01%. Caspase-3protein levels was increased after24h octreotide treatment.Tumors developed in all animals injected Huh-7cells. After daily injection of OCT for28consecutive days, the tumor volume was significantly reduced compared with controls (injected with physiological salinevehicle alone). The average tumor volume of octreotide-treated mice was131±60.04mm3versus206±53.71mm3in controls. Compared with control group, the MVD of octreotide treatment group was decreased by microvascular counting afer CD31immunohistochemical staining.ConclusionIn vitro, octreotide is able to significantly inhibit the growth of Huh-7cells, induce cell cycle arrest and apoptosis, And Caspase way may be involve in it; In vivo, octreotide inbibits the growth of liver cancer and tumor angiogenesis, may become a new therapy drug and improve the prognosis of HCC. |
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