[Anti-tumor effect of gene-viral therapeutic system CNHK300-murine endostatin on nude mouse gastric cancer].
OBJECTIVE
To investigate the anti-tumor effect of a novel gene-viral therapeutic system CNHK300-murine endostatin (CNHK300-mE) on gastric cancer.


METHODS
SGC-7901 gastric cancer cells (5 x 10(7) cells/mouse) were injected s.c. into the right flank of Balb/c nude mice, grown to 4-5 mm to demonstrate tumor take, and 10(9) pfu/100 microl CNHK300-mE virus was injected into tumors. Tumor sizes were measured with calipers every other day. Serum samples were obtained by retro-orbital puncture and level of endostatin expression in serum was quantitated by ELISA. Fifteen days after treatment, all mice were sacrificed and tumors were excised for immunohistochemical staining of PCNA, hexon and vWF. Tumor cell apoptosis was detected by TUNEL method.


RESULTS
From the 7th day post-treatment, the bearing tumors of mice treated with CNHK300-mE were significantly smaller than those of control group treated with PBS. Seven days after treatment, expression of endostatin was (2115 +/- 770) ng/ml, significantly higher than that of control group. Immunohistochemical staining indicated that hexon was expressed in treated tumor cells, and PCNA LI (label index) [(55.0+/-1.4)% vs control (74.1 +/- 0.4)%, P<0.05], microvessel density (MVD) of CNHK300-mE treated tumors decreased significantly. Apoptosis obviously increased in tumor cells[(78.4 +/- 9.1)% vs control (15.2 +/- 0.5)%, P<0.01]. Apoptosis bodies and crystal grid were found in tumor cell nuclear by electron microscope.


CONCLUSIONS
Gene-viral therapeutic system CNHK300-murine endostatin can replicate in gastric cancer cells. The mouse endostatin gene cloned into CNHK300-mE expressed in high level. CNHK300-mE may induce tumor cells apoptosis, reduce the expression of PCNA and efficiently suppress gastric cancer growth through inhibiting tumor angiogenesis.
Nie
Ming-Ming
MM
Department of General Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China. niemm88@hotmail.com
Fang
Guo-En
GE
Wang
Xing-Hua
XH
Su
Chang-Qing
CQ
Qian
Qi-Jun
QJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D043169:Endostatins / Q000235:genetics*; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013274:Stomach Neoplasms / Q000628:therapy*; D019098:Telomerase / Q000235:genetics; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D043169:Endostatins; D019098:Telomerase