[Experimental study of NK4 gene targeted therapy mediated by human telomerase reverse transcriptase promoter for colon cancer].
OBJECTIVE
To investigate anti-tumor effect of the recombined adenovirus encoding NK4 gene regulated by human telomerase reverse transcriptase (HTERT) promoter (Ad HTERTp-NK4) on human colon cancer.


METHODS
Colon cell line HCT116 was infected with Ad HTERTp-NK4. NK4 expression was determined by RT-PCR and Western blot. The cell-growth inhibition rate and the invasive capacity of cells were evaluated by MTT method and reconstituted basement membrane invasion assay. The model of subcutaneous tumor was generated by injection of HCT116 cells into the dorsum of nude mice. Ad HTERTp-NK4 was injected around the tumor tissues, and tumor growth was observed.


RESULTS
NK4 gene was highly expressed in infected HCT116 cells. The cell growth inhibition rate and the invasive inhibition rate in Ad HTERTp-NK4 cells were 47.14% and 40.63% respectively, which were significantly higher than those in the control cells (2.75% and 2.31%, P<0.05). Tumor growth was significantly inhibited in mice injected with Ad HTERTp-NK4, and the tumor growth inhibition rate was 47.3%, which was significantly higher than that in the controls (4.6%, P<0.05).


CONCLUSIONS
Ad HTERTp-NK4 can inhibit tumor growth and decrease the invasive capacity of tumor cells, which makes it an ideal candidate for new gene therapy for colon carcinoma.
Department of General Surgery, The First Municipal People's Hospital of Guangzhou, Guangzhou Medical College, Guangzhou 510180, China.
Bo
B
Xu
Huan-qing
HQ
Xiao
Shan-qi
SQ
Zeng
Gui-tian
GT
Huang
Zhen-bang
ZB
Liu
Yue-jun
YJ
Qian
Shu-hua
SH
Li
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
C509186:TERT protein, human; D019098:Telomerase