title: Effective targeting of colorectal cancer cells using TORC1/2 kinase inhibitors in vitro and in vivo.
abstract: OBJECTIVE
  We investigated the effects of TORC1/2 kinase inhibitors on colorectal cancer (CRC) cell lines.
  
  
  METHODS
  Using selective TORC1/2 inhibitors, rapamycin and PP242, we assessed their effect on the growth of CRC cells in vitro and tumor growth in vivo.
  
  
  RESULTS
  Rapamycin and PP242 inhibit proliferation and induce apoptosis of CRC cells. They also enhance proapoptotic effect of conventional chemo drug doxorubicin in CRC cells in vitro. When combined with doxorubicin, rapamycin and PP242 almost completely inhibit tumor growth in vivo. Rapamycin and PP242 inhibit phosphorylation of Akt, ribosomal S6 kinase, 4EBP1 and mTOR.
  
  
  CONCLUSIONS
  Our study suggests rapamycin and PP242 may be a useful therapeutic agent and inhibiting mTOR signaling pathway represents a new targeted therapy for CRC.
authors.affiliation: The Affiliated Hospital of Nantong University, Nantong 226001, China.|School of Medicine, Nantong University, Nantong 226019, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, The Third People's Hospital of Nantong, Nantong 226001, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: School of Medicine, Nantong University, Nantong 226019, China.
authors.forename: Juan-Juan
authors.initials: JJ
authors.lastname: Wu
authors.affiliation: Department of Paediatrics, The Second Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Oncological Surgery, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou 325001, China.
authors.forename: Ji-Xian
authors.initials: JX
authors.lastname: Cheng
authors.affiliation: The Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.affiliation: School of Medicine, Nantong University, Nantong 226019, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Yang
authors.affiliation: The Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Deng-Fu
authors.initials: DF
authors.lastname: Yao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D051379:Mice; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D046912:Multiprotein Complexes; D047428:Protein Kinase Inhibitors; D011687:Purines; D004317:Doxorubicin; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases; C572919:PP242; D020123:Sirolimus
keywords: PP242; colorectal cancer; mTOR signaling pathway; rapamycin