PMID- 31415285
OWN - NLM
STAT- MEDLINE
DCOM- 20200925
LR  - 20200925
IS  - 1473-5741 (Electronic)
IS  - 0959-4973 (Linking)
VI  - 30
IP  - 8
DP  - 2019 Sep
TI  - Ginsenoside Rd reverses cisplatin resistance in non-small-cell lung cancer A549 
      cells by downregulating the nuclear factor erythroid 2-related factor 2 pathway.
PG  - 838-845
LID - 10.1097/CAD.0000000000000781 [doi]
AB  - Clinical drug resistance to platinum-based chemotherapy is considered a major 
      impediment in the successful treatment of non-small-cell lung cancer (NSCLC). The 
      nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway regulates 
      the oxidative stress response, and in many cancer types, the high constitutive 
      expression of NRF2 leads to proliferation and chemoresistance. Ginsenoside Rd 
      (GS-Rd) is the main active component of ginsenosides. Here, GS-Rd was found to 
      inhibit the proliferation of A549 lung cancer cells and induce G0/G1 phase 
      arrest. We established cisplatin (DDP)-resistant A549 cell lines (A549/DDP). The 
      half maximal inhibitory concentrations of DDP, gemcitabine, and adriamycin were 
      much higher in A549/DDP cells than in A549 cells. The A549/DDP cell lines 
      developed multidrug resistance, accompanied by activation of multidrug resistance 
      protein 1 and multidrug resistance-associated protein 1, as well as NRF2 and its 
      target genes. Treatment with GS-Rd inhibited the NRF2 pathway and significantly 
      sensitized A549/DDP cells to therapeutic drugs. In addition, NRF2 knockdown 
      attenuated the synergistic effects of GS-Rd in both A549 and A54/DDP cells. Taken 
      together, these data show that NRF2 plays an important role in acquired drug 
      resistance in NSCLC, and GS-Rd may ameliorate this chemoresistance by 
      downregulating the NRF2 pathway. This study demonstrates that the NRF2 pathway 
      may serve as a therapeutic target in NSCLC, and ginseng compounds may be 
      effective for the treatment of this disease.
FAU - Chian, Song
AU  - Chian S
AD  - The Criminal Science and Technology Department, Zhejiang Police College.
FAU - Zhao, Yanna
AU  - Zhao Y
AD  - Institution of Hematology Research, The First Affiliated Hospital of Zhejiang 
      Chinese Medical University, Hangzhou, Zhejiang Province, People's Republic of 
      China.
FAU - Xu, Ming
AU  - Xu M
AD  - Institution of Hematology Research, The First Affiliated Hospital of Zhejiang 
      Chinese Medical University, Hangzhou, Zhejiang Province, People's Republic of 
      China.
FAU - Yu, Xiaoling
AU  - Yu X
AD  - Institution of Hematology Research, The First Affiliated Hospital of Zhejiang 
      Chinese Medical University, Hangzhou, Zhejiang Province, People's Republic of 
      China.
FAU - Ke, Xing
AU  - Ke X
AD  - The Criminal Science and Technology Department, Zhejiang Police College.
FAU - Gao, Ruilan
AU  - Gao R
AD  - Institution of Hematology Research, The First Affiliated Hospital of Zhejiang 
      Chinese Medical University, Hangzhou, Zhejiang Province, People's Republic of 
      China.
FAU - Yin, Liming
AU  - Yin L
AD  - Institution of Hematology Research, The First Affiliated Hospital of Zhejiang 
      Chinese Medical University, Hangzhou, Zhejiang Province, People's Republic of 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Anticancer Drugs
JT  - Anti-cancer drugs
JID - 9100823
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Ginsenosides)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - Q20Q21Q62J (Cisplatin)
RN  - WB232T95AV (ginsenoside Rd)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis
MH  - Biomarkers, Tumor/metabolism
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/metabolism/pathology
MH  - Cell Cycle
MH  - Cell Proliferation
MH  - Cisplatin/*pharmacology
MH  - Drug Resistance, Neoplasm/*drug effects
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Ginsenosides/*pharmacology
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/metabolism/pathology
MH  - NF-E2-Related Factor 2/*antagonists & inhibitors
MH  - Tumor Cells, Cultured
EDAT- 2019/08/16 06:00
MHDA- 2020/09/26 06:00
CRDT- 2019/08/16 06:00
PHST- 2019/08/16 06:00 [entrez]
PHST- 2019/08/16 06:00 [pubmed]
PHST- 2020/09/26 06:00 [medline]
AID - 00001813-201909000-00009 [pii]
AID - 10.1097/CAD.0000000000000781 [doi]
PST - ppublish
SO  - Anticancer Drugs. 2019 Sep;30(8):838-845. doi: 10.1097/CAD.0000000000000781.