AIM: To investigate the uptake of 99mTc-HYNIC-Tyr3-octreotide (99mTc-HYNIC-TOC) in human hepatocellular carcinoma (HCC), which can provide the localizable diagnosis in hepatic carcinoma. METHODS: The expression of som...AIM: To investigate the uptake of 99mTc-HYNIC-Tyr3-octreotide (99mTc-HYNIC-TOC) in human hepatocellular carcinoma (HCC), which can provide the localizable diagnosis in hepatic carcinoma. METHODS: The expression of somatostatin receptor 2 (SSTR2) messenger RNA (mRNA) in human HCC cell line HepG2 was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). Uptake of 99mTc-HYNIC-TOC was evaluated in the human HCC implanted into BALB/c nude mice. ANMIS2000 nuclear medicine analysis system was used to calculate the ratio of 99mTc uptake between tumor tissue and vital organs. RESULTS: We demonstrated the expression of SSTR2 mRNA in human HCC cell line HepG2 by RT-PCR. The size of the RT-PCR products was 364 bp detected by sequence analysis of the human SSTR2 mRNA. Scintigraphy proved that 99mTc-HYNIC-TOC was uptaken in the tumor tissue, liver and kidney of the tumor-bearing mice. CONCLUSION: Based on expression of the SSTR2 mRNA in human HCC, 99mTc-HYNIC-TOC can markedly bind with and be uptaken by human HCC tissues as compared with normal liver tissue. The significant retention of radionudide in kidney and bladder is probably related to non-specific peptide uptake in the tubulus cells of kidney and possibly due to excretion by kidney. Our results show that localizable diagnosis and targeting radiotherapy with radionuclide-labeled somatostatin analog for HCC are of great value to be further studied.展开更多
AIM: To investigate the therapeutic effect of somatostatin receptor type 2 (SSTR2) gene transfection on pancreatic carcinoma xenografts in vivo in experimental cancers. METHODS: Human pancreatic cancer cell line Panc-...AIM: To investigate the therapeutic effect of somatostatin receptor type 2 (SSTR2) gene transfection on pancreatic carcinoma xenografts in vivo in experimental cancers. METHODS: Human pancreatic cancer cell line Panc-1 was inoculated subcutaneously into the back of nude mice. When tumor nodules were grown as large as about 5 mmx5 mm days after inoculation, the mice were randomly divided into 3 groups (6 mice in each group). Group Ⅰ served as untreated control group. Group Ⅱ received an intratumoral injection of a combination of human cytomegalovirus promoter-6C (pCMV-6C) and lipofectamine 2000. Group Ⅲ received an intratumoral injection of a combination of pCMV-6C-SSTR2 and lipofectamine 2000. The rate of tumor growth was compared among these three groups. The expression of SSTR2 in these tumors was detected by immunohistochemistry and Western-blot. Apoptosis index (AI) in these tumors was examined by using TUNEL in situ. RESULTS: Intratumoral injection of a combination of pCMV-6C-SSTR2 and lipofectamine 2000 resulted in the expression of SSTR2 protein. The tumor size and weight in group Ⅲ (0.318±0.098 cm3, and 0.523±0.090 g, respectively) were significantly lower than those in group I (2.058±0.176 cms, and 1.412±0.146 g, respectively) and group Ⅱ (2.025±0.163 cm3, and 1.365±0.116 g, respectively) (P<0.05) The AI in group Ⅲ (1.47±0.13%) was significantly higher than that in groupⅠ(0.56±0.09%) and group Ⅱ (0.57±0.11%) (P<0.05). But there were no significant differences between groups Ⅰ and Ⅱ. CONCLUSION: Our data demonstrate that re-expression of SSTR2 gene has antitumor effects on experimental pancreatic cancer. Restoration of SSTR2 gene expression through gene transfer in vivo might be a potential gene therapy strategy for human pancreatic cancer.展开更多
The inhibition of metastatic progression of Somatostatin receptor type 2 （SSTR2） gene transfection mediated by adenovirus in human pancreatic carcinoma cells and the mechanisms involved in this effect were studied. ...The inhibition of metastatic progression of Somatostatin receptor type 2 （SSTR2） gene transfection mediated by adenovirus in human pancreatic carcinoma cells and the mechanisms involved in this effect were studied. The full-length human SSTR2 cDNA was introduced into the pancreatic cancer cell line BXPC-3 by adenovirus-mediated transfection. Stable expression of mRNAs and protein of SSTR2 was detected by RT-PCR and Western-blot. The Matrigel-coated Transwell was used to detect the migratory and invasive ability of SSTR2-expressing cells, Adv-GFP control cells and mock control cells. Furthermore, the expression of matrix metalloproteinase-2 （MMP-2） and tissue inhibitor of metalloproteinase-2 （TIMP-2） was detected by RT-PCR in these cells. The stable expression of SSTR2 was detected in BXPC-3 transfected by Adv-GFP-SSTR2. A dramatic decrease of BXPC-3 expressing sst2 cells migrating through a Matrigel-coated filter was observed, as compared with Adv-GFP control and mock control cells （P〈0. 01）. Moreover, the expression of MMP-2 mRNA was significantly reduced in the SSTR2-expressing cells and converse- ly the expression of TIMP-2 mRNA was significantly increased in the SSTR2-expressing cells when compared with the Adv-GFP control and mock control （P〈0. 01）. The expression of reintroduced human SSTR2 gene in BXPC-3 cells by Adv-GFP-SSTR2 had the anti-migratory and anti-invasive effects, and the mechanisms involved in this effect may be due to the down-regulated expression of MMP-2 and up-regulated expression of TIMP-2.展开更多
文摘AIM: To investigate the uptake of 99mTc-HYNIC-Tyr3-octreotide (99mTc-HYNIC-TOC) in human hepatocellular carcinoma (HCC), which can provide the localizable diagnosis in hepatic carcinoma. METHODS: The expression of somatostatin receptor 2 (SSTR2) messenger RNA (mRNA) in human HCC cell line HepG2 was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). Uptake of 99mTc-HYNIC-TOC was evaluated in the human HCC implanted into BALB/c nude mice. ANMIS2000 nuclear medicine analysis system was used to calculate the ratio of 99mTc uptake between tumor tissue and vital organs. RESULTS: We demonstrated the expression of SSTR2 mRNA in human HCC cell line HepG2 by RT-PCR. The size of the RT-PCR products was 364 bp detected by sequence analysis of the human SSTR2 mRNA. Scintigraphy proved that 99mTc-HYNIC-TOC was uptaken in the tumor tissue, liver and kidney of the tumor-bearing mice. CONCLUSION: Based on expression of the SSTR2 mRNA in human HCC, 99mTc-HYNIC-TOC can markedly bind with and be uptaken by human HCC tissues as compared with normal liver tissue. The significant retention of radionudide in kidney and bladder is probably related to non-specific peptide uptake in the tubulus cells of kidney and possibly due to excretion by kidney. Our results show that localizable diagnosis and targeting radiotherapy with radionuclide-labeled somatostatin analog for HCC are of great value to be further studied.
基金Supported by National Natural Science Foundation of China, No. 30271473
文摘AIM: To investigate the therapeutic effect of somatostatin receptor type 2 (SSTR2) gene transfection on pancreatic carcinoma xenografts in vivo in experimental cancers. METHODS: Human pancreatic cancer cell line Panc-1 was inoculated subcutaneously into the back of nude mice. When tumor nodules were grown as large as about 5 mmx5 mm days after inoculation, the mice were randomly divided into 3 groups (6 mice in each group). Group Ⅰ served as untreated control group. Group Ⅱ received an intratumoral injection of a combination of human cytomegalovirus promoter-6C (pCMV-6C) and lipofectamine 2000. Group Ⅲ received an intratumoral injection of a combination of pCMV-6C-SSTR2 and lipofectamine 2000. The rate of tumor growth was compared among these three groups. The expression of SSTR2 in these tumors was detected by immunohistochemistry and Western-blot. Apoptosis index (AI) in these tumors was examined by using TUNEL in situ. RESULTS: Intratumoral injection of a combination of pCMV-6C-SSTR2 and lipofectamine 2000 resulted in the expression of SSTR2 protein. The tumor size and weight in group Ⅲ (0.318±0.098 cm3, and 0.523±0.090 g, respectively) were significantly lower than those in group I (2.058±0.176 cms, and 1.412±0.146 g, respectively) and group Ⅱ (2.025±0.163 cm3, and 1.365±0.116 g, respectively) (P<0.05) The AI in group Ⅲ (1.47±0.13%) was significantly higher than that in groupⅠ(0.56±0.09%) and group Ⅱ (0.57±0.11%) (P<0.05). But there were no significant differences between groups Ⅰ and Ⅱ. CONCLUSION: Our data demonstrate that re-expression of SSTR2 gene has antitumor effects on experimental pancreatic cancer. Restoration of SSTR2 gene expression through gene transfer in vivo might be a potential gene therapy strategy for human pancreatic cancer.
文摘The inhibition of metastatic progression of Somatostatin receptor type 2 （SSTR2） gene transfection mediated by adenovirus in human pancreatic carcinoma cells and the mechanisms involved in this effect were studied. The full-length human SSTR2 cDNA was introduced into the pancreatic cancer cell line BXPC-3 by adenovirus-mediated transfection. Stable expression of mRNAs and protein of SSTR2 was detected by RT-PCR and Western-blot. The Matrigel-coated Transwell was used to detect the migratory and invasive ability of SSTR2-expressing cells, Adv-GFP control cells and mock control cells. Furthermore, the expression of matrix metalloproteinase-2 （MMP-2） and tissue inhibitor of metalloproteinase-2 （TIMP-2） was detected by RT-PCR in these cells. The stable expression of SSTR2 was detected in BXPC-3 transfected by Adv-GFP-SSTR2. A dramatic decrease of BXPC-3 expressing sst2 cells migrating through a Matrigel-coated filter was observed, as compared with Adv-GFP control and mock control cells （P〈0. 01）. Moreover, the expression of MMP-2 mRNA was significantly reduced in the SSTR2-expressing cells and converse- ly the expression of TIMP-2 mRNA was significantly increased in the SSTR2-expressing cells when compared with the Adv-GFP control and mock control （P〈0. 01）. The expression of reintroduced human SSTR2 gene in BXPC-3 cells by Adv-GFP-SSTR2 had the anti-migratory and anti-invasive effects, and the mechanisms involved in this effect may be due to the down-regulated expression of MMP-2 and up-regulated expression of TIMP-2.
