PMID- 36091811
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220913
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Ivermectin and gemcitabine combination treatment induces apoptosis of pancreatic 
      cancer cells via mitochondrial dysfunction.
PG  - 934746
LID - 10.3389/fphar.2022.934746 [doi]
LID - 934746
AB  - Pancreatic cancer is an aggressive cancer characterized by high mortality and 
      poor prognosis, with a survival rate of less than 5 years in advanced stages. 
      Ivermectin, an antiparasitic drug, exerts antitumor effects in various cancer 
      types. This is the first study to evaluate the anticancer effects of the 
      combination of ivermectin and gemcitabine in pancreatic cancer. We found that the 
      ivermectin-gemcitabine combination treatment suppressed pancreatic cancer more 
      effectively than gemcitabine alone treatment. The ivermectin-gemcitabine 
      combination inhibited cell proliferation via G1 arrest of the cell cycle, as 
      evidenced by the downregulation of cyclin D1 expression and the mammalian target 
      of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT-3) 
      signaling pathway. Ivermectin-gemcitabine increased cell apoptosis by inducing 
      mitochondrial dysfunction via the overproduction of reactive oxygen species and 
      decreased the mitochondrial membrane potential. This combination treatment also 
      decreased the oxygen consumption rate and inhibited mitophagy, which is important 
      for cancer cell death. Moreover, in vivo experiments confirmed that the 
      ivermectin-gemcitabine group had significantly suppressed tumor growth compared 
      to the gemcitabine alone group. These results indicate that ivermectin exerts 
      synergistic effects with gemcitabine, preventing pancreatic cancer progression, 
      and could be a potential antitumor drug for the treatment of pancreatic cancer.
CI  - Copyright (c) 2022 Lee, Kang, Kim, Kim, Jeong, Hong, Fang, Kim, Lee, Kim and Park.
FAU - Lee, Da Eun
AU  - Lee DE
AD  - Department of Surgery, Gangnam Severance Hospital, Yonsei University College of 
      Medicine, Seoul, South Korea.
AD  - Department of Medical Science, Graduate School of Medical Science, Brain Korea 21 
      Project, Yonsei University College of Medicine, Seoul, South Korea.
FAU - Kang, Hyeon Woong
AU  - Kang HW
AD  - Department of Surgery, Gangnam Severance Hospital, Yonsei University College of 
      Medicine, Seoul, South Korea.
AD  - Department of Medical Science, Graduate School of Medical Science, Brain Korea 21 
      Project, Yonsei University College of Medicine, Seoul, South Korea.
FAU - Kim, So Yi
AU  - Kim SY
AD  - Department of Surgery, Gangnam Severance Hospital, Yonsei University College of 
      Medicine, Seoul, South Korea.
AD  - Department of Medical Science, Graduate School of Medical Science, Brain Korea 21 
      Project, Yonsei University College of Medicine, Seoul, South Korea.
FAU - Kim, Myeong Jin
AU  - Kim MJ
AD  - Department of Surgery, Gangnam Severance Hospital, Yonsei University College of 
      Medicine, Seoul, South Korea.
AD  - Department of Medical Science, Graduate School of Medical Science, Brain Korea 21 
      Project, Yonsei University College of Medicine, Seoul, South Korea.
FAU - Jeong, Jae Woong
AU  - Jeong JW
AD  - Department of Medicine, Yonsei University College of Medicine, Seoul, South 
      Korea.
FAU - Hong, Woosol Chris
AU  - Hong WC
AD  - Department of Surgery, Gangnam Severance Hospital, Yonsei University College of 
      Medicine, Seoul, South Korea.
AD  - Department of Medical Science, Graduate School of Medical Science, Brain Korea 21 
      Project, Yonsei University College of Medicine, Seoul, South Korea.
FAU - Fang, Sungsoon
AU  - Fang S
AD  - Department of Medical Science, Graduate School of Medical Science, Brain Korea 21 
      Project, Yonsei University College of Medicine, Seoul, South Korea.
FAU - Kim, Hyung Sun
AU  - Kim HS
AD  - Department of Surgery, Gangnam Severance Hospital, Yonsei University College of 
      Medicine, Seoul, South Korea.
FAU - Lee, Yun Sun
AU  - Lee YS
AD  - Department of Surgery, Gangnam Severance Hospital, Yonsei University College of 
      Medicine, Seoul, South Korea.
AD  - Department of Medical Science, Graduate School of Medical Science, Brain Korea 21 
      Project, Yonsei University College of Medicine, Seoul, South Korea.
FAU - Kim, Hyo Jung
AU  - Kim HJ
AD  - Department of Surgery, Gangnam Severance Hospital, Yonsei University College of 
      Medicine, Seoul, South Korea.
FAU - Park, Joon Seong
AU  - Park JS
AD  - Department of Surgery, Gangnam Severance Hospital, Yonsei University College of 
      Medicine, Seoul, South Korea.
LA  - eng
PT  - Journal Article
DEP - 20220826
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC9459089
OTO - NOTNLM
OT  - apoptosis
OT  - gemcitabine
OT  - ivermectin
OT  - mitochondrial dysfunction
OT  - pancreatic cancer
OT  - reactive oxygen species
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- 2022/09/13 06:00
MHDA- 2022/09/13 06:01
PMCR- 2022/08/26
CRDT- 2022/09/12 04:07
PHST- 2022/05/03 00:00 [received]
PHST- 2022/08/02 00:00 [accepted]
PHST- 2022/09/12 04:07 [entrez]
PHST- 2022/09/13 06:00 [pubmed]
PHST- 2022/09/13 06:01 [medline]
PHST- 2022/08/26 00:00 [pmc-release]
AID - 934746 [pii]
AID - 10.3389/fphar.2022.934746 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Aug 26;13:934746. doi: 10.3389/fphar.2022.934746. 
      eCollection 2022.