title: Targeting TGF-β1 and AKT signal on growth and metastasis of anaplastic thyroid cancer cell in vivo.
abstract: We have recently reported that therapies targeting TGF-β1 signaling were effective to prevent the anaplastic thyroid cancer (ATC) cell growth, but not the invasion. Phosphatidylinositol 3-kinase (PI3K)/AKT signaling are activated in ATC and play a major role in ATC invasion. Herein, we examined the effects of targeting TGF-β1 by shRNA in combination with pan-AKT inhibitor, MK-2206 on growth and metastasis of ATC xenografts implanted in severe combined immunodeficient mice.
  
  
  
  8505C cells or 8505C/shRNA cells or 8505C/TGF-β1 shRNA cells were implanted sc in 5-week-old female nude mice. Upon establishment of palpable tumours, MK-2206 was administered at 60 mg/kg, orally, three times a week for 6 weeks.
  
  
  
  The results showed that TGF-β1/shRNA alone only prevents anaplastic thyroid cancer (ATC) tumor formation, but not lung metastasis. MK-2206 alone only inhibits lung metastasis, but not tumor formation. The combined treatment with TGF-β1/shRNA and MK-2206 led to an approximately 71% growth inhibition compared with TGF-β1/shRNA (44%) and MK-2206 (15%). The combined treatment with TGF-β1/shRNA and MK-2206 significantly inhibits lung metastasis.
  
  
  
  These findings demonstrated that targeting TGF-β1 in combination with MK-2206 was the effective method for treatment of ATC.
authors.affiliation: Department of General Surgery, Department of Pathology; the Affiliated Hospital of Qingdao University, Qingdao, China. zkejun@yahoo.ca.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: F-Y
authors.initials: FY
authors.lastname: Hao
authors.forename: K-J
authors.initials: KJ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction; D065646:Thyroid Carcinoma, Anaplastic / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D053773:Transforming Growth Factor beta1; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt