Antitumor bioactivity of adenovirus-mediated p27mt in colorectal cancer cell line SW480.
OBJECTIVE
To explore the antitumor bioactivity of adenovirus-mediated mutant type p27(kip1) gene in a colorectal cancer cell line SW480.


METHODS
We constructed recombinant adenovirus vector expressing a mutant type p27(kip1) gene (ad-p27mt), with mutation of Thr-187/Pro-188 (ACGCCC) to Met-187/Ile-188 (ATGATC), and transduced into SW480 cells. Then we detected expression of p27, Bcl-2 and Bax protein in the transductants by Western blotting, cell cycle of transductants by a digital flow cytometric system, migrating potential with Boyden Chamber and SW480 tumor cell growth inhibition in vitro and in vivo.


RESULTS
We found that a recombinant adenovirus vector of expressing ad-p27mt, with mutation of Thr-187/Pro-188 (ACGCCC) to Met-187/Ile-188 (ATGATC) has potent inhibition of SW480 tumor cell growth in vitro and in vivo. Furthermore, ad-p27mt induced cell apoptosis via regulating bax and bcl-2 expressions, and G(1)/S arrest in SW480 cells and inhibited cell migration.


CONCLUSIONS
ad-p27mt has a strong anti-tumor bioactivity and has the potential to develop into new therapeutic agents for colorectal cancer.
Gastroenterology Department of Zhongnan Hospital, Wuhan University, Hubei Province, China.
Ze-Qun
ZQ
Sun
Chang-Sheng
CS
Deng
Shao-Yong
SY
Xu
Yong
Y
Du
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009154:Mutation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494826:BAX protein, human; C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27