PMID- 31081049
OWN - NLM
STAT- MEDLINE
DCOM- 20190830
LR  - 20211204
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Print)
IS  - 1019-6439 (Linking)
VI  - 54
IP  - 6
DP  - 2019 Jun
TI  - Icariin enhances the chemosensitivity of cisplatin‑resistant ovarian cancer cells 
      by suppressing autophagy via activation of the AKT/mTOR/ATG5 pathway.
PG  - 1933-1942
LID - 10.3892/ijo.2019.4785 [doi]
AB  - Icariin is a flavonoid derived from Epimedium sagittatum, and has a wide range of 
      biological and pharmacological effects; however, little is known regarding its 
      effect on drug‑resistant ovarian cancer and the signal transduction pathways 
      underlying the regulation of apoptosis and autophagy. The present study aimed to 
      investigate the re‑sensitization effects of icariin exerted on an ovarian cancer 
      cell line. Autophagy was analyzed in a SKVCR cell line that had been treated with 
      icariin. We investigated the sensitivity of SKVCR cells to cisplatin, as well as 
      the effects of an autophagy agonist (rapamycin) on autophagy, apoptosis, and the 
      protein kinase B (AKT) signaling pathway. Finally, the mechanism underlying the 
      effects of autophagy‑related (ATG) protein ATG5 overexpression on autophagy, 
      apoptosis and AKT signaling in SKVCR cells were determined. The results revealed 
      that treatment with icariin inhibited cell viability and autophagy, but promoted 
      G0/G1 phase cell cycle arrest and apoptosis as determined by Cell Counting Kit‑8, 
      immunofluorescence and flow cytometry assays, respectively. Icariin reduced the 
      resistance of SKVCR cells to cisplatin in vitro by inducing G1/S cell cycle 
      transition, apoptosis and inhibiting autophagy. Furthermore, enhanced autophagy 
      induced by rapamycin treatment or overexpression of ATG5 partially reversed the 
      effect of icariin on cisplatin resistance and autophagy in SKVCR cells. At the 
      molecular level, rapamycin treatment or overexpression of ATG5 reversed the 
      effects of icariin on the expression of autophagy‑associated proteins, including 
      microtubule‑associated protein 1 light chain 3beta, Beclin‑1, ATG5 and p62, and the 
      AKT/mammalian target of rapamycin (mTOR) pathway. Collectively, our results 
      suggested that icariin enhances the chemosensitivity of SKVCR cells by 
      suppressing autophagy via activation of the AKT/mTOR signaling pathway.
FAU - Jiang, Shaoyan
AU  - Jiang S
AD  - Department of Pharmacy, Shenzhen Maternity and Child Healthcare Hospital, 
      Shenzhen, Guangdong 518028, P.R. China.
FAU - Chang, Hong
AU  - Chang H
AD  - Department of Pharmacy, Shenzhen Maternity and Child Healthcare Hospital, 
      Shenzhen, Guangdong 518028, P.R. China.
FAU - Deng, Shaojie
AU  - Deng S
AD  - Department of Pharmacy, Shenzhen Maternity and Child Healthcare Hospital, 
      Shenzhen, Guangdong 518028, P.R. China.
FAU - Fan, Danyi
AU  - Fan D
AD  - Department of Pharmacy, Shenzhen Maternity and Child Healthcare Hospital, 
      Shenzhen, Guangdong 518028, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20190415
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (ATG5 protein, human)
RN  - 0 (Autophagy-Related Protein 5)
RN  - 0 (Flavonoids)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - Q20Q21Q62J (Cisplatin)
RN  - VNM47R2QSQ (icariin)
SB  - IM
MH  - Autophagy/*drug effects
MH  - Autophagy-Related Protein 5/metabolism
MH  - Cell Cycle/drug effects
MH  - Cell Cycle Checkpoints
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Cisplatin/*pharmacology
MH  - Drug Resistance, Neoplasm/*drug effects
MH  - Drug Screening Assays, Antitumor
MH  - Drug Synergism
MH  - Female
MH  - Flavonoids/*pharmacology
MH  - Humans
MH  - Ovarian Neoplasms/drug therapy/*metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC6521925
EDAT- 2019/05/14 06:00
MHDA- 2019/08/31 06:00
PMCR- 2019/04/15
CRDT- 2019/05/14 06:00
PHST- 2018/01/30 00:00 [received]
PHST- 2018/12/12 00:00 [accepted]
PHST- 2019/05/14 06:00 [entrez]
PHST- 2019/05/14 06:00 [pubmed]
PHST- 2019/08/31 06:00 [medline]
PHST- 2019/04/15 00:00 [pmc-release]
AID - ijo-54-06-1933 [pii]
AID - 10.3892/ijo.2019.4785 [doi]
PST - ppublish
SO  - Int J Oncol. 2019 Jun;54(6):1933-1942. doi: 10.3892/ijo.2019.4785. Epub 2019 Apr 
      15.