PMID- 34345262
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210806
IS  - 1792-1015 (Electronic)
IS  - 1792-0981 (Print)
IS  - 1792-0981 (Linking)
VI  - 22
IP  - 3
DP  - 2021 Sep
TI  - Sorafenib prevents the proliferation and induces the apoptosis of liver cancer 
      cells by regulating autophagy and hypoxia-inducible factor-1.
PG  - 980
LID - 10.3892/etm.2021.10412 [doi]
LID - 980
AB  - Sorafenib has been approved as a systemic drug for advanced liver cancer; 
      however, the underlying mechanisms remain unclear. The present study aimed to 
      investigate the effects of sorafenib on the proliferation, autophagy and 
      apoptosis of HepG2 cells under hypoxia. Briefly, reverse 
      transcription-quantitative PCR and western blotting was performed to quantify 
      HIF-1, LC3II/I, mTOR and p70s6K expression levels. Cell proliferation was 
      determined using the Cell Counting Kit-8 assay and the cell apoptosis rate was 
      evaluated using flow cytometry. The results demonstrated that autophagy and 
      apoptosis were induced by hypoxia, and that sorafenib further enhanced 
      hypoxia-induced autophagy and apoptosis in HepG2 cells in a dose-dependent 
      manner. Furthermore, the mechanism of sorafenib-mediated autophagy in liver 
      cancer cell were investigated by using chloroquine (CQ). The results showed that 
      CQ significantly inhibited autophagy by decreasing LC3II/LC3I ratio in HepG2 
      cells treated with sorafenib and/or hypoxia. By contrast, sorafenib could 
      increase the expression of hypoxia-inducible factor-1 (HIF-1) and of the 
      autophagy marker (LC3II/I) and decrease the expression of mammalian target of 
      rapamycin and p70 ribosomal S6 kinase in HepG2 cells under normoxia and hypoxia 
      conditions, suggesting that sorafenib could induce hypoxia and autophagy in liver 
      cancer cells. In addition, sorafenib was demonstrated to prevent proliferation 
      and induce apoptosis of HepG2 cells under normoxia and hypoxia. Sorafenib could 
      also prevent the malignant behavior of HepG2 by inducing hypoxia and autophagy. 
      In summary, the findings from the present study suggested that sorafenib may 
      inhibit liver cancer progression by activating autophagy and HIF-1 signaling 
      pathway.
CI  - Copyright: (c) Yang et al.
FAU - Yang, Qingzhuang
AU  - Yang Q
AD  - Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital of 
      Hainan Medical University, Haikou, Hainan 570102, P.R. China.
FAU - Gao, Lianghui
AU  - Gao L
AD  - Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital of 
      Hainan Medical University, Haikou, Hainan 570102, P.R. China.
FAU - Huang, Xiaolong
AU  - Huang X
AD  - Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital of 
      Hainan Medical University, Haikou, Hainan 570102, P.R. China.
FAU - Weng, Jie
AU  - Weng J
AD  - Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital of 
      Hainan Medical University, Haikou, Hainan 570102, P.R. China.
FAU - Chen, Youke
AU  - Chen Y
AD  - Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital of 
      Hainan Medical University, Haikou, Hainan 570102, P.R. China.
FAU - Lin, Shibu
AU  - Lin S
AD  - Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital of 
      Hainan Medical University, Haikou, Hainan 570102, P.R. China.
FAU - Yin, Qiushi
AU  - Yin Q
AD  - Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital of 
      Hainan Medical University, Haikou, Hainan 570102, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20210712
PL  - Greece
TA  - Exp Ther Med
JT  - Experimental and therapeutic medicine
JID - 101531947
PMC - PMC8311259
OTO - NOTNLM
OT  - autophagy
OT  - hypoxia
OT  - hypoxia-inducible factor-1alpha
OT  - liver cancer
OT  - sorafenib
COIS- The authors declare that they have no competing interests.
EDAT- 2021/08/05 06:00
MHDA- 2021/08/05 06:01
PMCR- 2021/07/12
CRDT- 2021/08/04 07:06
PHST- 2020/05/04 00:00 [received]
PHST- 2021/03/29 00:00 [accepted]
PHST- 2021/08/04 07:06 [entrez]
PHST- 2021/08/05 06:00 [pubmed]
PHST- 2021/08/05 06:01 [medline]
PHST- 2021/07/12 00:00 [pmc-release]
AID - ETM-0-0-10412 [pii]
AID - 10.3892/etm.2021.10412 [doi]
PST - ppublish
SO  - Exp Ther Med. 2021 Sep;22(3):980. doi: 10.3892/etm.2021.10412. Epub 2021 Jul 12.