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Ivermectin and gemcitabine combination treatment induces apoptosis of pancreatic cancer cells via mitochondrial dysfunction

 Da Eun Lee  ;  Hyeon Woong Kang  ;  So Yi Kim  ;  Myeong Jin Kim  ;  Jae Woong Jeong  ;  Woosol Chris Hong  ;  Sungsoon Fang  ;  Hyung Sun Kim  ;  Yun Sun Lee  ;  Hyo Jung Kim  ;  Joon Seong Park 
 FRONTIERS IN PHARMACOLOGY, Vol.13 : 934746, 2022-08 
Journal Title
Issue Date
apoptosis ; gemcitabine ; ivermectin ; mitochondrial dysfunction ; pancreatic cancer ; reactive oxygen species
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.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyung Sun(김형선) ORCID logo https://orcid.org/0000-0002-9002-3569
Kim, Hyo Jung(김효정) ORCID logo https://orcid.org/0000-0002-3514-1247
Park, Joon Seong(박준성) ORCID logo https://orcid.org/0000-0001-8048-9990
Fang, Sungsoon(황성순) ORCID logo https://orcid.org/0000-0003-0201-5567
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