PURPOSE: To develop a model of X-linked inhibitor of apoptosis (XIAP) down regulation in colorectal cancer cell lines. This may be used to determine whether combination strategies have clinical potential. METHODS: A series of clones were developed using short hairpin RNA (shRNA) against XIAP stably expressed in HCT116 cells. XIAP mRNA and protein levels were established by RT-PCR and Immunoblot, respectively. GeneChip microarrays confirmed XIAP knockdown and absence of compensation by other IAP members. RESULTS: Four XIAP knockdown cell lines show 82-93% reduction in XIAP mRNA and 67-89% reduction in protein when compared to four luciferase control cell lines. XIAP knockdown sensitises cells to rhTRAIL by a factor of 3, to paclitaxel and docetaxel by a factor of >2 and, to a lesser extent, radiotherapy (20% enhancement). CONCLUSIONS: Clinical trials with XIAP antisense continue, and these data suggest combination studies with agents such as rhTRAIL and taxanes should be undertaken.
PURPOSE: To develop a model of X-linked inhibitor of apoptosis (XIAP) down regulation in colorectal cancer cell lines. This may be used to determine whether combination strategies have clinical potential. METHODS: A series of clones were developed using short hairpin RNA (shRNA) against XIAP stably expressed in HCT116 cells. XIAP mRNA and protein levels were established by RT-PCR and Immunoblot, respectively. GeneChip microarrays confirmed XIAP knockdown and absence of compensation by other IAP members. RESULTS: Four XIAP knockdown cell lines show 82-93% reduction in XIAP mRNA and 67-89% reduction in protein when compared to four luciferase control cell lines. XIAP knockdown sensitises cells to rhTRAIL by a factor of 3, to paclitaxel and docetaxel by a factor of >2 and, to a lesser extent, radiotherapy (20% enhancement). CONCLUSIONS: Clinical trials with XIAP antisense continue, and these data suggest combination studies with agents such as rhTRAIL and taxanes should be undertaken.
Authors: Mandana T Manzari; Gray R Anderson; Kevin H Lin; Ryan S Soderquist; Merve Çakir; Mitchell Zhang; Chandler E Moore; Rachel N Skelton; Maréva Fèvre; Xinghai Li; Joseph J Bellucci; Suzanne E Wardell; Simone A Costa; Kris C Wood; Ashutosh Chilkoti Journal: Sci Adv Date: 2019-09-04 Impact factor: 14.136
Authors: T Trarbach; M Moehler; V Heinemann; C-H Köhne; M Przyborek; C Schulz; V Sneller; G Gallant; S Kanzler Journal: Br J Cancer Date: 2010-01-12 Impact factor: 7.640