PMID- 34499759
OWN - NLM
STAT- MEDLINE
DCOM- 20220502
LR  - 20220524
IS  - 1098-2299 (Electronic)
IS  - 0272-4391 (Linking)
VI  - 83
IP  - 2
DP  - 2022 Apr
TI  - Astragaloside IV enhances the sensibility of lung adenocarcinoma cells to 
      bevacizumab by inhibiting autophagy.
PG  - 461-469
LID - 10.1002/ddr.21878 [doi]
AB  - Bevacizumab (BV) has an inhibitory effect on tumor growth including lung 
      adenocarcinoma. However, its efficacy is greatly affected by drug resistance. 
      Astragaloside IV (AST-IV) is effective in combination with other drugs is 
      effective to treat cancer. This study aimed to investigate the effect of AST-IV 
      on enhancing the sensibility of lung adenocarcinoma cells to BV. A549 cells were 
      treated by different concentrations of BV and AST-IV. Cell viability, cell cycle, 
      and apoptosis were detected by thiazolyl blue tetrazolium bromide (MTT) and flow 
      cytometry, respectively. Quantitative reverse transcription-polymerase chain 
      reaction (qRT-PCR) and western blotting were performed to detect the expression 
      levels of autophagy- and apoptosis-related proteins, protein kinase B (AKT), and 
      mammalian target of rapamycin (mTOR). The results showed that BV or AST-IV could 
      inhibit the viability and promote the apoptosis of A549 cells in a 
      concentration-dependent manner. Moreover, BV or AST-IV inhibited Bcl-2 expression 
      and increased the expressions of Bax and Cleaved caspase-3, and promoted 
      apoptosis. BV and AST-IV in combination acted synergistically on viability and 
      apoptosis of A549 cells. However, BV alone down-regulated P62 expression, 
      LC3I/LC3II level, the number of cells arrested at S phase and the phosphorylation 
      levels of AKT and mTOR, but upregulated the number of cells arrested at G0/G1 
      phase and Beclin1 expression, whereas AST-IV alone could reverse the effect of BV 
      on autophagy-related proteins, the phosphorylation levels of AKT and mTOR. This 
      paper demonstrates that AST-IV enhances the effect of BV on inhibiting 
      proliferation and promoting apoptosis of lung adenocarcinoma cells through 
      inhibiting autophagy pathway.
CI  - (c) 2021 Wiley Periodicals, LLC.
FAU - Li, Liang
AU  - Li L
AD  - Department of Thoracic Surgery, Hainan General Hospital, Haikou, China.
FAU - Li, Gao
AU  - Li G
AD  - Department of Thoracic Surgery, Hainan General Hospital, Haikou, China.
FAU - Chen, Minbiao
AU  - Chen M
AD  - Department of Thoracic Surgery, Hainan General Hospital, Haikou, China.
FAU - Cai, Renzhong
AU  - Cai R
AUID- ORCID: 0000-0001-5564-3079
AD  - Department of Thoracic Surgery, Hainan General Hospital, Haikou, China.
LA  - eng
PT  - Journal Article
DEP - 20210909
PL  - United States
TA  - Drug Dev Res
JT  - Drug development research
JID - 8204468
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Saponins)
RN  - 0 (Triterpenes)
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - 3A592W8XKE (astragaloside A)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - *Adenocarcinoma of Lung/drug therapy
MH  - Apoptosis
MH  - Apoptosis Regulatory Proteins
MH  - Autophagy
MH  - Bevacizumab/pharmacology
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Humans
MH  - *Lung Neoplasms/drug therapy
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Saponins
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Triterpenes
OTO - NOTNLM
OT  - apoptosis
OT  - astragaloside
OT  - autophagy
OT  - bevacizumab
OT  - proliferation
EDAT- 2021/09/10 06:00
MHDA- 2022/05/03 06:00
CRDT- 2021/09/09 17:25
PHST- 2021/08/24 00:00 [revised]
PHST- 2020/11/16 00:00 [received]
PHST- 2021/08/24 00:00 [accepted]
PHST- 2021/09/10 06:00 [pubmed]
PHST- 2022/05/03 06:00 [medline]
PHST- 2021/09/09 17:25 [entrez]
AID - 10.1002/ddr.21878 [doi]
PST - ppublish
SO  - Drug Dev Res. 2022 Apr;83(2):461-469. doi: 10.1002/ddr.21878. Epub 2021 Sep 9.