PMID- 32905663
OWN - NLM
STAT- MEDLINE
DCOM- 20210727
LR  - 20240226
IS  - 1742-7843 (Electronic)
IS  - 1742-7835 (Linking)
VI  - 128
IP  - 2
DP  - 2021 Feb
TI  - Bufalin inhibits ovarian carcinoma via targeting mTOR/HIF-alpha pathway.
PG  - 224-233
LID - 10.1111/bcpt.13487 [doi]
AB  - Ovarian cancer is a severe health threat for women with increased incidence and 
      stymied development in diagnosis and therapy. Drug resistance is still a big 
      challenge. Bufalin is a multi-functional steroid-like compound extracted from 
      natural product Chansu and has been tested as antitumour agent recently. The 
      application and mechanism of bufalin in ovarian cancer remain unclear yet. 
      Bufalin was first examined in ovarian epithelial cancer cell as well as primary 
      ovarian tissue to evaluate its inhibitory activity in cell growth and migration, 
      followed by the validation in xenograft tumour model and the patient samples. 
      Bufalin is well tolerated by normal ovarian tissue at up to 40 muM and suppresses 
      the cell growth and migration at 10 muM and xenograft tumour growth at 0.1mg/kg 
      dosage. Bufalin inhibits the mammalian target of rapamycin (mTOR) activation and 
      subsequently decreases hypoxia-induced factor 1 alpha (HIF-1alpha) level. 
      Overexpression of HIF-1alpha could abolish the pro-apoptotic and antimigration 
      activity of bufalin in cell culture. Strikingly, low HIF-1alpha level was correlated 
      with improved responsiveness to cisplatin treatment in ovarian cancer patients. 
      Bufalin was a potent inhibitor of cell growth and migration in ovarian cancer 
      cells through suppression of mTOR activation and HIF-1alpha induction. Bufalin could 
      be used to enhance the efficacy of cisplatin in ovarian cancer patients.
CI  - (c) 2020 Nordic Association for the Publication of BCPT (former Nordic 
      Pharmacological Society).
FAU - Su, Shan
AU  - Su S
AD  - Department of Gynecology, Zibo Central Hospital, Shandong, China.
FAU - Dou, Hongtao
AU  - Dou H
AD  - Department of Gynecology, Zibo Central Hospital, Shandong, China.
FAU - Wang, Zhe
AU  - Wang Z
AD  - Department of Obstetrical, Zibo Maternal and Child Health Hospital, Shandong, 
      China.
FAU - Zhang, Qinghua
AU  - Zhang Q
AUID- ORCID: 0000-0001-5606-4191
AD  - Department of Gynecology, Zibo Central Hospital, Shandong, China.
LA  - eng
PT  - Journal Article
DEP - 20201002
PL  - England
TA  - Basic Clin Pharmacol Toxicol
JT  - Basic & clinical pharmacology & toxicology
JID - 101208422
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Bufanolides)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - Q20Q21Q62J (Cisplatin)
RN  - U549S98QLW (bufalin)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Antineoplastic Combined Chemotherapy Protocols/pharmacology
MH  - Bufanolides/*pharmacology
MH  - Carcinoma, Ovarian Epithelial/*drug therapy/enzymology/genetics/pathology
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cisplatin/pharmacology
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Mice, Nude
MH  - Neoplasm Invasiveness
MH  - Ovarian Neoplasms/*drug therapy/enzymology/genetics/pathology
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Tumor Burden/drug effects
MH  - Tumor Cells, Cultured
MH  - Xenograft Model Antitumor Assays
MH  - Mice
OTO - NOTNLM
OT  - HIF-1alpha
OT  - bufalin
OT  - cisplatin
OT  - mTOR
OT  - ovarian cancer
EDAT- 2020/09/10 06:00
MHDA- 2021/07/28 06:00
CRDT- 2020/09/09 18:16
PHST- 2020/05/26 00:00 [received]
PHST- 2020/08/21 00:00 [revised]
PHST- 2020/09/02 00:00 [accepted]
PHST- 2020/09/10 06:00 [pubmed]
PHST- 2021/07/28 06:00 [medline]
PHST- 2020/09/09 18:16 [entrez]
AID - 10.1111/bcpt.13487 [doi]
PST - ppublish
SO  - Basic Clin Pharmacol Toxicol. 2021 Feb;128(2):224-233. doi: 10.1111/bcpt.13487. 
      Epub 2020 Oct 2.