PMID- 35422963
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220416
IS  - 1943-8141 (Print)
IS  - 1943-8141 (Electronic)
IS  - 1943-8141 (Linking)
VI  - 14
IP  - 3
DP  - 2022
TI  - CDK4/6 inhibitor enhances the radiosensitization of esophageal squamous cell 
      carcinoma (ESCC) by activating autophagy signaling via the suppression of mTOR.
PG  - 1616-1627
AB  - OBJECTIVE: To investigate the radiosensitizing effect of cyclin D-cyclin 
      dependent kinase (CDK) 4/6 inhibitor palbociclib on esophageal squamous cell 
      carcinoma (ESCC) and its underlying mechanisms. METHODS: The effect of 
      palbociclib on ESCC cell radiosensitivity was detected by cell counting kit-8 
      (CCK-8) and clonogenic assay. gammaH2AX immunofluorescent staining was used to assess 
      the repair of DNA damage induced by radiation. The expression of DNA repair 
      proteins were examined by western blotting. Subsequently, immunoblotting and 
      autophagy inhibitors were used to evaluate the underlying mechanisms of 
      palbociclib triggered radiosensitization. Finally, the xenografts of ESCC were 
      established to study the radiosensitizing effect of palbociclib in vivo. RESULTS: 
      Palbociclib combined with irradiation significantly inhibited the cell viability 
      of ESCC in vitro. The expression level of gammaH2AX showed that radiation induced DNA 
      damage repair was inhibited by palbociclib treatment. Palbociclib also suppressed 
      the expression of RAD51 and phosphorylated DNA-dependent protein kinase catalytic 
      subunit (p-DNA-PKcs) after irradiation. Mechanically, palbociclib enhanced the 
      radiosensitization of ESCC by activating autophagy via suppression of mammalian 
      target of rapamycin (mTOR). Inhibition of autophagy using chloroquine could 
      partially reverse the radiation enhancing effect of palbociclib. Lastly, the 
      xenografted tumor experiment confirmed the radiosensitizing effect of palbociclib 
      in ESCC in vivo. CONCLUSION: Our results showed that palbociclib improved the 
      radiosensitivity of ESCC in vivo and in vitro, and thus it may be a promising 
      radiosensitization agent for the treatment of ESCC.
CI  - AJTR Copyright (c) 2022.
FAU - Qin, Wen-Jun
AU  - Qin WJ
AD  - Department of Radiation Oncology, General Hospital of Ningxia Medical University 
      Yinchuan 750004, Ningxia, China.
AD  - Graduate School, Ningxia Medical University Yinchuan 750004, Ningxia, China.
AD  - Cancer Institute, Ningxia Medical University Yinchuan 750004, Ningxia, China.
FAU - Su, Yi-Ge
AU  - Su YG
AD  - Graduate School, Ningxia Medical University Yinchuan 750004, Ningxia, China.
FAU - Ding, Xiao-Long
AU  - Ding XL
AD  - Graduate School, Ningxia Medical University Yinchuan 750004, Ningxia, China.
FAU - Zhao, Ren
AU  - Zhao R
AD  - Department of Radiation Oncology, General Hospital of Ningxia Medical University 
      Yinchuan 750004, Ningxia, China.
AD  - Cancer Institute, Ningxia Medical University Yinchuan 750004, Ningxia, China.
FAU - Zhao, Zhi-Jun
AU  - Zhao ZJ
AD  - Department of Laboratory Medicine, General Hospital of Ningxia Medical University 
      Yinchuan 750004, Ningxia, China.
FAU - Wang, Yan-Yang
AU  - Wang YY
AD  - Department of Radiation Oncology, General Hospital of Ningxia Medical University 
      Yinchuan 750004, Ningxia, China.
AD  - Graduate School, Ningxia Medical University Yinchuan 750004, Ningxia, China.
AD  - Cancer Institute, Ningxia Medical University Yinchuan 750004, Ningxia, China.
LA  - eng
PT  - Journal Article
DEP - 20220315
PL  - United States
TA  - Am J Transl Res
JT  - American journal of translational research
JID - 101493030
PMC - PMC8991149
OTO - NOTNLM
OT  - CDK4/6 inhibitor
OT  - autophagy
OT  - esophageal squamous cell carcinoma
OT  - radiosensitization
COIS- None.
EDAT- 2022/04/16 06:00
MHDA- 2022/04/16 06:01
PMCR- 2022/03/15
CRDT- 2022/04/15 05:24
PHST- 2021/11/08 00:00 [received]
PHST- 2022/01/27 00:00 [accepted]
PHST- 2022/04/15 05:24 [entrez]
PHST- 2022/04/16 06:00 [pubmed]
PHST- 2022/04/16 06:01 [medline]
PHST- 2022/03/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Transl Res. 2022 Mar 15;14(3):1616-1627. eCollection 2022.