PMID- 36266920
OWN - NLM
STAT- MEDLINE
DCOM- 20231222
LR  - 20231222
IS  - 2045-7634 (Electronic)
IS  - 2045-7634 (Linking)
VI  - 12
IP  - 5
DP  - 2023 Mar
TI  - NBDHEX re-sensitizes adriamycin-resistant breast cancer by inhibiting glutathione 
      S-transferase pi.
PG  - 5833-5845
LID - 10.1002/cam4.5370 [doi]
AB  - PURPOSE: Adriamycin is a novel chemotherapeutic agent of great benefit for 
      treating breast cancer. However, adriamycin -resistance remains a major obstacle. 
      The vital Glutathione transferase P1 (GSTPi) inhibitor 
      6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol (NBDHEX) has recently shown 
      antitumor activity in various cancers. In this study, we analyzed the effect of 
      NBDHEX and adriamycin combination against breast cancer in vitro and in vivo. 
      METHODS: CCK-8 assay was performed to test cell viability. The location and 
      expression level of GSTpi was determined by immunofluorescence and Western blot 
      in cells and immunohistochemistry staining in tissues. The enzyme activity test 
      was applied to detect the effect of NBDHEX on the activity of GSTpi. The 
      apoptosis related proteins' expression was tested using Western blot. The 
      phosphorylation sites of GSTpi were detected by mass spectrometry. Antitumor 
      effects of single treatment or co-administration of adriamycin and NBDHEX were 
      evaluated in nude mice. RESULTS: NBDHEX treatment inhibited GSTpi enzyme activity 
      and co-administration of adriamycin and NBDHEX promoted apoptosis of 
      adriamycin-resistance breast cancer cell. Moreover, drug combination of NBDHEX 
      and adriamycin significantly enhanced tumor growth inhibition compared with 
      single agent. CONCLUSION: NBDHEX serves as a good candidate for combination with 
      adriamycin, offering new insights for breast cancer treatment.
CI  - (c) 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
FAU - Sha, Huanhuan
AU  - Sha H
AD  - Department of Chemotherapy, Jiangsu Cancer Hospital, The Affiliated Cancer 
      Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research, 
      Nanjing, Jiangsu, China.
FAU - Zou, Renrui
AU  - Zou R
AD  - The Fourth Clinical School of The Affiliated Cancer Hospital of Nanjing Medical 
      University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, 
      Nanjing, Jiangsu, China.
FAU - Lu, Ya
AU  - Lu Y
AD  - The Fourth Clinical School of The Affiliated Cancer Hospital of Nanjing Medical 
      University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, 
      Nanjing, Jiangsu, China.
FAU - Gan, Yujie
AU  - Gan Y
AD  - The Fourth Clinical School of The Affiliated Cancer Hospital of Nanjing Medical 
      University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, 
      Nanjing, Jiangsu, China.
FAU - Ma, Rong
AU  - Ma R
AD  - Research Center of Clinical Oncology, Jiangsu Cancer Hospital, The Affiliated 
      Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer 
      Research, Nanjing, Jiangsu, China.
FAU - Feng, Jifeng
AU  - Feng J
AUID- ORCID: 0000-0002-9300-4312
AD  - The Fourth Clinical School of The Affiliated Cancer Hospital of Nanjing Medical 
      University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, 
      Nanjing, Jiangsu, China.
FAU - Chen, Dan
AU  - Chen D
AD  - Research Center of Clinical Oncology, Jiangsu Cancer Hospital, The Affiliated 
      Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer 
      Research, Nanjing, Jiangsu, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221020
PL  - United States
TA  - Cancer Med
JT  - Cancer medicine
JID - 101595310
RN  - EC 2.5.1.18 (Glutathione S-Transferase pi)
RN  - 0 (6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol)
RN  - 0 (Oxadiazoles)
RN  - 0 (Antineoplastic Agents)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - *Glutathione S-Transferase pi
MH  - Animals
MH  - Mice
MH  - *Oxadiazoles
MH  - *Breast Neoplasms/drug therapy
MH  - Antineoplastic Agents/therapeutic use
MH  - Mice, Nude
MH  - *Doxorubicin/therapeutic use
PMC - PMC10028113
OTO - NOTNLM
OT  - GSTpi
OT  - NBDHEX
OT  - adriamycin
OT  - breast cancer
OT  - resistant
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2022/10/22 06:00
MHDA- 2023/03/24 06:00
PMCR- 2022/10/20
CRDT- 2022/10/21 01:12
PHST- 2022/08/26 00:00 [revised]
PHST- 2021/12/15 00:00 [received]
PHST- 2022/10/08 00:00 [accepted]
PHST- 2022/10/22 06:00 [pubmed]
PHST- 2023/03/24 06:00 [medline]
PHST- 2022/10/21 01:12 [entrez]
PHST- 2022/10/20 00:00 [pmc-release]
AID - CAM45370 [pii]
AID - 10.1002/cam4.5370 [doi]
PST - ppublish
SO  - Cancer Med. 2023 Mar;12(5):5833-5845. doi: 10.1002/cam4.5370. Epub 2022 Oct 20.