Octreotide acts as an antitumor angiogenesis compound and suppresses tumor growth in nude mice bearing human hepatocellular carcinoma xenografts.

PURPOSE: To investigate the effect of octreotide on angiogenesis induced by human hepatocellular carcinoma (HCC) and to evaluate whether octreotide can suppress tumor growth in nude mice bearing human HCC xenografts through inhibition of angiogenesis. METHODS: Using MTT assay, invasion assay, migration assay, and Matrigel assay, the effects of octreotide on endothelial cells stimulated by vascular endothelial growth factor (VEGF) were evaluated in vitro. MTT assay was also used to investigate the effects of octreotide on human HCC cells with high (MHCC97-H) and low (MHCC97-L) metastatic potential that were established from the animal model of human HCC LCI-D20 in nude mice. The expression of somatostatin receptor (SSTR) subtypes in human umbilical vein endothelial cells (HUVECs), MHCC97-H, and MHCC97-L cells was detected by RT-PCR analysis. An LCI-D20 corneal micropocket model in nude mice was used to evaluate the effect of octreotide on angiogenesis induced by human HCC in vivo. Male nude mice were subcutaneously implanted with LCI-D20 tumor tissues for the tumor xenograft studies. Microvessel density was analyzed in CD34-stained tumor sections by the immunohistochemical SP method. RESULTS: In vitro, octreotide inhibited the proliferation, invasion, and differentiation of HUVECs elicited by VEGF. RT-PCR analysis demonstrated that HUVECs expressed the somatostatin receptor subtype SSTR3. In vivo, octreotide was sufficiently potent to suppress nude mice corneal neovascularization induced by tumor tissues from LCI-D20. Systemic administrations of octreotide produced a significant suppression of the growth of LCI-D20. In cell culture, MHCC97-H and MHCC97-L cells were insensitive to octreotide at concentrations that significantly inhibited endothelial cells proliferation. The HCC cells used did not express any known SSTRs. Immunohistochemical studies of tumor tissues revealed decreased microvessel density in octreotide-treated animals as compared with controls. CONCLUSIONS: The present study demonstrates that the somatostatin analogue octreotide is a potent antitumor angiogenesis compound and the antiproliferative effect of octreotide on tumor growth in nude mice bearing HCC xenografts may be mediated, at least in part, by its suppressive effect on blood vessel supply. The somatostatin analogue octreotide might provide a useful and relatively nontoxic adjuvant therapy in the treatment of HCC.

Small-diameter prosthetic H-graft portacaval shunts in the treatment of portal hypertension.

BACKGROUND: Portasystemic shunts, especially total shunts, are effective tools for reducing portal pressure and controlling variceal bleeding but lead to high risk of encephalopathy and accelerating liver failure. The purpose of this study is to evaluate the clinical effects of small-diameter expanded polytetrafluoroethylene (ePTFE) H-graft portacaval shunts in the treatment of portal hypertension. METHODS: Thirty-one patients with portal hypertension were treated with ePTFE small-diameter H-graft portacaval shunts from December 1995 to April 2002. Twenty-one had externally ringed grafts and 10 had non-ringed grafts; 20 had 10 mm diameter grafts and 11 had 8 mm grafts. The left gastric artery and coronary vein were ligated in 22 patients. Additionally, 6 patients underwent pericardial devascularization, and splenectomies were performed on 30 patients. RESULTS: An average decrease of free portal pressure (FPP) from (32.13 +/- 4.86) cmH2O before shunting to (12.55 +/- 5.57) cmH2O after shunting was observed. Portal blood flow was reduced by 1/3 compared with the levels measured before shunting. Twenty-eight patients survived after the operation, and no upper gastrointestinal rebleeding occurred in the follow-up period (40.2 months on average). We lost contact with one patient. Color Doppler ultrasonography and/or portography revealed the shunts to be patent in 28 cases and occluded in 2 (6.4%) cases. Encephalopathy developed in 4 patients (12.9%). CONCLUSION: Small-diameter ePTFE H-graft portacaval shunts can effectively reduce portal pressure. Moreover, the majority of the hepatopetal flow from the portal vein can be adequately maintained. The reinforced shunts may achieve a higher rate of patency. Morbidity from encephalopathy was less frequent than in patients receiving total shunts. Small-diameter H-graft portacaval shunts are also effective in preventing recurrent variceal bleeding.

Effect of reorganized-human growth hormone on cell cycle kinetics in liver cancer in vitro.

OBJECTIVE: To study the effect of reorganized-human growth hormone (r-hGH) on cycle kinetics and apoptosis of liver cancer cells or 7402 cells. METHODS: Liver cancer cells were cultured for 24 hours with r-hGH at different concentrations with or without cisplatin (DDP). Cells undergoing apoptosis and differentiation were determined by flow cytometry (FCM). RESULTS: Comparison of the results in culture with and without r-hGH showed that the percentage of cells in G0-G1 phase dropped (P<0.05), whereas in S phase increased (P<0.05). Adding of r-hGH and DDP to the culture medium increased the apoptosis of liver cancer cells more significantly than adding DDP only (P<0.05). CONCLUSIONS: Liver cancer cells might express the hGH receptor. In vitro r-hGH might induce the differentiation of liver cancer cells, stimulate the combination of DNA, and reduce the cells in G0-G1 phases. These improve the sensibility of tumors to the special-staged chemical treatment. Chemotherapy together with r-hGH may increase the apoptosis of liver cancer cells.