bcl-xs gene therapy induces apoptosis of human mammary tumors in nude mice
Ealovega, M.W.; McGinnis, P.K.; Sumantran, V.N.; Clarke, M.F.; Wicha, M.S.
Cancer Research 56(9): 1965-1969
1996
ISSN/ISBN: 0008-5472 PMID: 8616832 Document Number: 461568
Bcl-x-s is a dominant negative repressor of Bcl-2 and BCl-x-L, both of which inhibit apoptosis. We used a replication-deficient adenoviral vector to transiently overexpress Bcl-x-s in MCF-7 human breast cancer cells, which overexpress Bcl-x-L. Infection with this vector induced apoptosis in vitro. We then determined the effects of intratumoral injection of bcl-x-s adenovirus on solid MCF-7 tumors in nude mice. Tumors injected four times with the bcl-x-s adenovirus showed a 50% reduction in size. Using terminal transferase-mediated dUTP-digoxigenin nick end labeling, we observed apoptotic cells at sites of bcl-x-s adenoviral injection. These experiments demonstrate the feasibility of using bcl-x-s gene therapy to induce apoptosis in human breast tumors.