Adenovirus-mediated FasL gene transfer into human gastric carcinoma.
OBJECTIVE
To evaluate the possible value of FasL in gastric cancer gene therapy by investigating the effects of FasL expression on human gastric cancer cell line.


METHODS
An adenoviral vector encoding the full-length human FasL cDNA was constructed and used to infect a human gastric cancer (SGC-7901) cell line. FasL expression was confirmed by X-gal staining, flow cytometric analysis and RT-PCR. The effect of FasL on cell proliferation was determined by clonogenic assay, cytotoxicity was detected by MTT assay, and cell viability was measured by trypan blue exclusion. The therapeutic efficiency of Ad-FasL in vivo was investigated with a xenograft tumor model in nude mice.


RESULTS
SGC-7901 cells infected with Ad-FasL showed increased expression of FasL, resulting in significantly decreased cell growth and colony-forming activity when compared with control adenovirus-infected cells. The cytotoxicity of anti-Fas antibody (CH-11) in gastric cancer cells was stronger than that of ActD (91+/-8 vs 60+/-5, P<0.01), and the cytotoxicity of Ad-FasL was stronger than that of CH-11 (60+/-5 vs 50+/-2, P<0.05). In addition, G1-phase arrest (67.75+/-0.39 vs 58.03+/-2.16, P<0.05) and apoptosis were observed in Ad-FasL-infected SGC-7901 cells, and the growth of SGC-7901 xenografts in nude mice was retarded after intra-tumoral injection with Ad-FasL (54% vs 0%, P<0.0001).


CONCLUSIONS
Infection of human gastric carcinoma cells with Ad-FasL induces apoptosis, indicating that this target gene might be of potential value in gene therapy for gastric cancer.
Zheng
Shi-Ying
SY
Department of Cardiothoracic Surgery, The First Affiliated Hospital of Suzhou University, Suzhou 215006, Jiangsu Province, China. syzheng88@sina.com
Li
De-Chun
DC
Zhang
Zhi-De
ZD
Zhao
Jun
J
Ge
Jin-Feng
JF
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002455:Cell Division; D045744:Cell Line, Tumor; D053222:Fas Ligand Protein; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D013274:Stomach Neoplasms / Q000628:therapy*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins