PMID- 19080079
OWN - NLM
STAT- MEDLINE
DCOM- 20090611
LR  - 20211203
IS  - 0376-2491 (Print)
IS  - 0376-2491 (Linking)
VI  - 88
IP  - 42
DP  - 2008 Nov 18
TI  - [Phosphatidylinositol 3-kinase/mammalian target of rapamycin pathway is critical 
      for survival and proliferation of pancreatic cancer stem-like side population 
      cells].
PG  - 2994-8
AB  - OBJECTIVE: To isolate and identify the side population (SP) cells in pancreatic 
      cancer and investigate the role of phosphatidylinositol 3-kinase/mammalian target 
      of rapamycin (PI3K/mTOR) pathway in the survival and proliferation of them. 
      METHODS: Pancreatic cancer cell of the lines PANC-1, BXPC-3, ASPC-1, PC-3, and 
      SW-1990 were cultured. Hoechst 33432 staining and fluorescence-activated cell 
      sorter (FACS) were used to sort the SP cells. Verapamil, inhibitor of ATP binding 
      cassette (ABC) transporter, was added before the Hoechst 33342 inoculation to 
      observe its influence on the SP proportion. Media with LY294002, specific 
      inhibitor of P13K, or rapamycin, specific inhibitor of mammalian target of 
      rapamycin (mTOR), were used to culture PANC-1 cells to observe the survival of 
      cells. Twenty-one NOD-SCID mice were randomly divided into 7 equal groups. Four 
      groups were inoculated subcutaneously with SP cells of the concentrations of 
      5x10(5), 5x10(4), 5x10(3), or 1x10(3) at the right axillary fossa and with non-SP 
      cells at the left then Hoechst 33342 staining, flow cytometric sorting were used 
      to detect the content of SP cells at the left axillary fossa. The other 3 groups 
      were injected subcutaneously with non-Hoechst 33342 treated cells of the 
      concentrations of 5x10(5), 5x10(4), 5x10(3), or 1x10(3) at the right axillary 
      fossa and PBS at the left axillary fossa. Ten weeks later the mice were killed to 
      undergo pathological examination. RESULTS: All cell lines were found to exhibit 
      verapamil-sensitive SP cells except BXPC-3 cells. The SP cell proportion of the 
      PANC-1 cells was 7.84%. No SP cell was found in the cells treated with verapamil. 
      The colony-formation ability of the SP cells was (43.7+/-3.1)%, significantly 
      higher than those of the non-SP cells and cells without Hoechst 33342 cells 
      [(8.3+/-1.6)% and (10.2+/-1.9)% respectively, both P=0.000]. The tumorigenic 
      ability of the SP cells was 100 times as those of the non-SP cells and Hoechst 
      33342 un-treated cells. After addition of LY294002 and rapamycin the fractions of 
      the SP cells in the in PANC-1 cells decreased from (7.60+/-0.27)% to 
      (1.90+/-0.22)% and (1.14+/-0.20)% respectively, both P=0.000, and they 
      preferentially inhibited the SP cells rather than non-SP cells. CONCLUSION: SP 
      cells are enriched in pancreatic cancer stem-like cells. PI3K/mTOR pathway is 
      critical for pancreatic SP cells maintenance that can be selected as a new target 
      for inhibiting cancer stem-like cells.
FAU - Zhou, Jing
AU  - Zhou J
AD  - Institute of Pancreatic Surgery, Union Hospital, Huazhong University of Science 
      and Technology, Wuhan 430022, China.
FAU - Wang, Chun-you
AU  - Wang CY
FAU - Liu, Tao
AU  - Liu T
FAU - Wu, He-shui
AU  - Wu HS
FAU - Zhou, Feng
AU  - Zhou F
FAU - Xiong, Jiong-xin
AU  - Xiong JX
FAU - Zhao, Gang
AU  - Zhao G
FAU - Yang, Ming
AU  - Yang M
FAU - Yin, Tao
AU  - Yin T
FAU - Zhou, Meng-tao
AU  - Zhou MT
LA  - chi
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Zhonghua Yi Xue Za Zhi
JT  - Zhonghua yi xue za zhi
JID - 7511141
RN  - 0 (Benzimidazoles)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - P976261J69 (bisbenzimide ethoxide trihydrochloride)
SB  - IM
MH  - Animals
MH  - Benzimidazoles/pharmacology
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Cell Survival
MH  - Humans
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Neoplastic Stem Cells/*cytology
MH  - Pancreatic Neoplasms/*pathology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Protein Kinases/*metabolism
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases
MH  - Xenograft Model Antitumor Assays
EDAT- 2008/12/17 09:00
MHDA- 2009/06/12 09:00
CRDT- 2008/12/17 09:00
PHST- 2008/12/17 09:00 [entrez]
PHST- 2008/12/17 09:00 [pubmed]
PHST- 2009/06/12 09:00 [medline]
PST - ppublish
SO  - Zhonghua Yi Xue Za Zhi. 2008 Nov 18;88(42):2994-8.