PMID- 35401195
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220413
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Silibinin Therapy Improves Cholangiocarcinoma Outcomes by Regulating 
      ERK/Mitochondrial Pathway.
PG  - 847905
LID - 10.3389/fphar.2022.847905 [doi]
LID - 847905
AB  - Background: Silibinin is widely utilized drug in various cancer treatments, 
      though its application in cholangiocarcinoma has not yet been explored. For the 
      first time, we evaluated the anticancer potential and underlying molecular 
      mechanism of silibinin in treatment of cholangiocarcinoma treatment. Methods: 
      HuCCT-1 and CCLP-1 cells were chosen to be an in vitro study model and were 
      exposed to various concentrations of silibinin for indicated times. Cell 
      viability was evaluated by the cell counting kit-8 (CCK-8) assay and half maximal 
      inhibitory (IC50) concentrations were calculated. Cell proliferation capacity was 
      determined through the use of colony formation and 5-Ethynyl-2'- deoxyuridine 
      (EdU) assays. Cell apoptosis and cycle arrest were assessed by Live/Dead staining 
      assay and flow cytometry (FCM). The protein levels of extracellular regulated 
      protein kinases (ERK)/mitochondrial apoptotic pathway were evaluated through 
      western blotting (WB). Mitochondrial membrane potential changes were determined 
      via 5,5',6,6'-Tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide (JC-1). A 
      cholangiocarcinoma cell line xenograft model was used to assess the anti-tumor 
      activity of silibinin in vivo. Results: Inhibition of the ERK protein by 
      silibinin led to a significant decrease in mitochondrial membrane potential, 
      which, in turn, caused Cytochrome C to be released from the mitochondria. The 
      activation of downstream apoptotic pathways led to apoptosis of 
      cholangiocarcinoma cells. In general, silibinin inhibited the growth of 
      cholangiocarcinoma cell line xenograft tumors. Conclusions: Silibinin is able to 
      inhibit cholangiocarcinoma through the ERK/mitochondrial apoptotic pathway, which 
      makes silibinin a potential anti-tumor drug candidate for cholangiocarcinoma 
      treatment.
CI  - Copyright (c) 2022 Bai, Chen, Hu, Wang, Wu and Yu.
FAU - Bai, Yang
AU  - Bai Y
AD  - Department of Surgery, The Second Affiliated Hospital, Zhejiang University School 
      of Medicine, Hangzhou, China.
AD  - Department of Hepatobiliary and Pancreatic Surgery, Affiliated Jinhua Hospital, 
      Zhejiang University School of Medicine, Jinhua, China.
FAU - Chen, Jiaqi
AU  - Chen J
AD  - Stomatology Hospital, School of Stomatology, Zhejiang University School of 
      Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key 
      Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of 
      Zhejiang University, Hangzhou, China.
FAU - Hu, Weijian
AU  - Hu W
AD  - Department of Hepatobiliary and Pancreatic Surgery, Affiliated Jinhua Hospital, 
      Zhejiang University School of Medicine, Jinhua, China.
FAU - Wang, Lei
AU  - Wang L
AD  - Department of Urology Surgery, Affiliated Jinhua Hospital, Zhejiang University 
      School of Medicine, Jinhua, China.
FAU - Wu, Yulian
AU  - Wu Y
AD  - Department of Surgery, The Second Affiliated Hospital, Zhejiang University School 
      of Medicine, Hangzhou, China.
FAU - Yu, Shi'an
AU  - Yu S
AD  - Department of Hepatobiliary and Pancreatic Surgery, Affiliated Jinhua Hospital, 
      Zhejiang University School of Medicine, Jinhua, China.
LA  - eng
PT  - Journal Article
DEP - 20220323
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8983842
OTO - NOTNLM
OT  - ERK
OT  - anti tumor drug
OT  - cholangiocarcinoma
OT  - mitochondrial membrane potential
OT  - silibinin
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/04/12 06:00
MHDA- 2022/04/12 06:01
PMCR- 2022/03/23
CRDT- 2022/04/11 05:27
PHST- 2022/01/03 00:00 [received]
PHST- 2022/03/07 00:00 [accepted]
PHST- 2022/04/11 05:27 [entrez]
PHST- 2022/04/12 06:00 [pubmed]
PHST- 2022/04/12 06:01 [medline]
PHST- 2022/03/23 00:00 [pmc-release]
AID - 847905 [pii]
AID - 10.3389/fphar.2022.847905 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Mar 23;13:847905. doi: 10.3389/fphar.2022.847905. 
      eCollection 2022.