Adenovirus Expressing Mutant p27
kip1
Enhanced Apoptosis and Inhibited the Growth of Xenografted Human Breast Cancer |
| |
Authors: | Tsuyoshi Sasaki Yu Katayose Kuniharu Yamamoto Masamichi Mizuma Satoru Shiraso Shinichi Yabuuchi Akira Oda Toshiki Rikiyama Masaya Oikawa Toru Onogawa Masanori Suzuki Choon-Taek Lee Michiaki Unno |
| |
Institution: | (1) Division of Hepato-Biliary Pancreatic Surgery, Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan;(2) Kamma Memorial Hospital, Nasushiobara, Japan;(3) Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea |
| |
Abstract: | Purpose To evaluate the anti-tumor effects of a novel adenovirus expressing mutant p27
kip1
(Adp27-mt), which consists of a mutation of Thr-187/Pro-188 to Met-187/Ile-188.
Methods Using the human breast cancer cell lines, MDA-MB-231, ZR-75-1, and MCF-7, we tested Adp27-mt for cell cycle assay, growth
inhibition assay, and TdT-mediated dUTP-biotin nick end labeling in a human breast cancer-grafted severe combined immunodeficiency
(SCID) mouse model.
Results The mutant p27
kip1
induced stronger apoptosis in the breast cancer cell lines than adenovirus expressing wild-type p27
kip1
(Adp27-wt). Adp27-mt inhibits cell growth significantly; being about 5- and 3.5-fold stronger for IC50 than Adp27-wt in the
breast cancer cell lines, MDA-MD-231 and ZR-75-1, respectively. In the human breast cancer-grafted SCID mouse model, Adp27-mt
induced tumor regression and antitumor effects significantly better than Adp27-wt. Furthermore, Adp27-mt mainly caused G2/M
arrest in the cell cycle progression, whereas Adp27-wt mediated a G1/S arrest 48 h after infection.
Conclusion The mutant p27
kip1
protein induced apoptosis, and inhibited cell growth more efficiently with stronger anti-tumor effects than wild-type p27
kip1
. Thus, the recombinant adenovirus expressing mutant p27
kip1
could be useful in gene therapy against breast cancer. |
| |
Keywords: | Adenovirus Mutant p27 kip1 Breast cancer |
本文献已被 PubMed SpringerLink 等数据库收录! |
|