[Induction of necrosis in the hepatocellular carcinoma HepG2 xenografts treated with SOM230].
OBJECTIVE
To investigate the effects of SOM230, a new somatostatin analogue, on the proliferation of hepatocellular carcinoma (HCC) cell line HepG2 in vitro and in vivo, and explore the mechanism underline the necrosis of tumors.


METHODS
MTT, TdT-mediated dUTP nick end labeling assay (TUNEL) and flow cytometric assay were used to measure the effects of SOM230 on the proliferation and apoptosis of HCC HepG2 cells. Nude mice bearing HCC xenografts of the HepG2 cell line were treated with SOM230 (100 microg/kg/d subcutaneously injection) and saline as a control for eight weeks. The mass and percentage of necrotic volume of the HCC xenografts in nude mice were determined. Western blot was used to detect SSTR2 in HCC xenografts. Immunohistochemical method was used to detect the expression sites of SSTR2 and VEGF in HCC xenografts. ELISA was used to detect the levels of TNFalpha.


RESULTS
No proliferation and apoptosis of HepG2 cells were induced by SOM230 in vitro (F = 0.16, P more than 0.05). The percentage of necrotic volume in SOM230 were significantly higher than that of control group (73.4%+/-7.0% vs 30.2%+/-14.0%, t = -8.02, P more than 0.01). SSTR2 was expressed in blood sinus of HCC xenografts in nude mice. There was no significance difference in the level of SSTR2 expression between SOM230 group and saline treated group. VEGF expression in xenografts was down-regulated by SOM230 treatment. SOM230 treatment did not affect the level of TNFalpha in HCC xenografts (t = -0.24, P more than 0.05).


CONCLUSIONS
SOM230 can induce massive necrosis of HCC xenografts only after the blockage of blood flow through down-regulation of VEGF mediated by SSTR2.
Xie
Yan
Y
Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China.
Chen
Shuang
S
Wang
Chun-Hui
CH
Tang
Cheng-Wei
CW
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011897:Random Allocation; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D017481:Receptors, Somatostatin; D042461:Vascular Endothelial Growth Factor A; D013004:Somatostatin; C517782:pasireotide