PMID- 23268708
OWN - NLM
STAT- MEDLINE
DCOM- 20130815
LR  - 20211021
IS  - 1557-8852 (Electronic)
IS  - 1084-9785 (Print)
IS  - 1084-9785 (Linking)
VI  - 28
IP  - 2
DP  - 2013 Mar
TI  - The tumor suppressor, p53, contributes to radiosensitivity of lung cancer cells 
      by regulating autophagy and apoptosis.
PG  - 153-9
LID - 10.1089/cbr.2012.1297 [doi]
AB  - PURPOSE: Cell death is one of the most important endpoints of radiosensitivity. 
      The tumor suppressor p53 participates not only in regulation of apoptosis, but 
      also in autophagy mechanism. In this study, H1299-P53 (with wild-type p53) and 
      H1299-175H (with mutant 175H) were used, and the effects of p53 on 
      radiosensitivity were analyzed. METHODS: Cell models with different p53 status 
      were established by gene engineering, and cell viability was examined by colony 
      formation assay, and cell counting kit-8 (CCK-8), 3-Methyladenine, and Z-VAD were 
      used to block autophagy and apoptosis, respectively. Western blot was used to 
      detect protein expression; monodansylcadaverine (MDC) staining was used to 
      analyze autophagy rate; DAPI/Propidium Iodide (PI) staining and flow cytometry 
      were used to assess apoptosis and necrosis. RESULTS: In parental H1299, 
      H1299-P53, and H1299-175H cells, radiosensitivity exhibited different by colony 
      formation and CCK-8 assay (D0: 1.764 Gy, 1.407 Gy and 1.695 Gy; Dq: 2.977 Gy, 
      1.199 Gy and 2.312 Gy in turn). The radiosensitization of p53 was associated with 
      the increase of MDM2 and P21 expression. The ionizing radiation (IR)-induced 
      apoptosis was significant in H1299-P53 compared with in H1299 and H199-175H (p < 
      0.05) by flow cytometry, and the expression of cleaved-caspase3 was increased in 
      H1299-P53 cells. While the IR-induced autophagy was significant in H1299 cells (p 
      < 0.01) and decreased in H1299-P53 and H1299-175H cells (p < 0.01) by MDC 
      staining, the expression of MAPLC3II and Beclin-1 increased in H1299, but not in 
      H1299-p53 and H199-175H cells. The IR-induced cell survival was significantly 
      increased by Z-VAD-FMK and decreased by 3MA in H1299-P53 cells; IR- induced 
      autophagy was significantly increased by Z-VAD-FMK in H1299-P53 cells (p < 0.01), 
      but not changed in H1299 cells. CONCLUSION: p53 could regulate radiosensitivity 
      by inhibiting autophagy and activating apoptosis; autophagy provides a 
      prosurvival mechanism, and p53 potently abrogated the IR-induced autophagy, while 
      mutant 175H shown no effect on radiosensitivity, suggesting that individual 
      treatment strategies should be based on p53 status in patients.
FAU - Cheng, Guanghui
AU  - Cheng G
AD  - Department of Radiation Oncology, China-Japan Union Hospital, Jilin University, 
      Changchun, China.
FAU - Kong, Dejuan
AU  - Kong D
FAU - Hou, Xue
AU  - Hou X
FAU - Liang, Bing
AU  - Liang B
FAU - He, Mengzi
AU  - He M
FAU - Liang, Nan
AU  - Liang N
FAU - Ma, Shumei
AU  - Ma S
FAU - Liu, Xiaodong
AU  - Liu X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121226
PL  - United States
TA  - Cancer Biother Radiopharm
JT  - Cancer biotherapy & radiopharmaceuticals
JID - 9605408
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - Apoptosis/*radiation effects
MH  - Autophagy/*radiation effects
MH  - Blotting, Western
MH  - Colony-Forming Units Assay
MH  - Humans
MH  - Lung Neoplasms/metabolism/*pathology/radiotherapy
MH  - Radiation Tolerance/*physiology
MH  - Transcriptional Activation
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p53/*genetics/*metabolism
MH  - X-Rays
PMC - PMC3589888
EDAT- 2012/12/28 06:00
MHDA- 2013/08/16 06:00
PMCR- 2014/03/01
CRDT- 2012/12/28 06:00
PHST- 2012/12/28 06:00 [entrez]
PHST- 2012/12/28 06:00 [pubmed]
PHST- 2013/08/16 06:00 [medline]
PHST- 2014/03/01 00:00 [pmc-release]
AID - 10.1089/cbr.2012.1297 [pii]
AID - 10.1089/cbr.2012.1297 [doi]
PST - ppublish
SO  - Cancer Biother Radiopharm. 2013 Mar;28(2):153-9. doi: 10.1089/cbr.2012.1297. Epub 
      2012 Dec 26.