PMID- 37963994
OWN - NLM
STAT- MEDLINE
DCOM- 20240423
LR  - 20240423
IS  - 1439-099X (Electronic)
IS  - 0179-7158 (Linking)
VI  - 200
IP  - 5
DP  - 2024 May
TI  - Osthole inhibits GSK-3beta/AMPK/mTOR pathway-controlled glycolysis and increases 
      radiosensitivity of subcutaneous transplanted hepatocellular carcinoma in nude 
      mice.
PG  - 444-452
LID - 10.1007/s00066-023-02173-8 [doi]
AB  - PURPOSE: Osthole possesses anti-tumor activities. However, whether osthole can 
      have a radiosensitization effect on hepatic cancer remains unclear. Here, an 
      HCC-LM3 cells-inoculated subcutaneous transplanted tumor was adopted to explore 
      the effect of osthole. METHODS: The tumor-bearing mice were treated with 
      100 mg/kg osthole for 12 days, 4 Gy irradiation twice, or their combination. The 
      tumor volume and weight, lactic acid content, glycolytic enzyme activities, and 
      protein expression of glycogen synthase kinase 3beta (GSK-3beta), p‑GSK-3beta, mammalian 
      target of rapamycin (mTOR), p‑mTOR, AMP-activated protein kinase (AMPK), p‑AMPK, 
      glucose transporter 1/3, and pyruvate kinase M2 were determined. The 
      GSK-3beta-overexpressed HCC-LM3 or SK-Hep‑1 cell models were also adopted to verify 
      the effects of osthole on expression of these proteins. RESULTS: The tumor volume 
      and weight, lactic acid content, and glycolytic enzyme activities in tumor 
      tissues were lower in the osthole + radiation group than in the radiation group. 
      Moreover, osthole could reverse the radiation-induced increments of 
      p‑GSK-3beta/GSK-3beta and p‑mTOR/mTOR protein ratios and the expression of glucose 
      transporter 1/3 and pyruvate kinase M2 proteins in tumor tissues, and increase 
      the protein ratio of p‑AMPK/AMPK. The effects of osthole on these 
      glycolysis-related proteins were also observed in GSK-3beta-overexpressed HCC-LM3 or 
      SK-Hep‑1 cell models. CONCLUSION: Osthole has a radiosensitizing effect on 
      subcutaneous transplanted hepatocellular carcinoma, and its mechanism may be 
      related to inhibition of GSK-3beta/AMPK/mTOR pathway-controlled glycolysis.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.
FAU - Huang, Hui
AU  - Huang H
AD  - College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu Province, 
      China.
FAU - Xue, Jie
AU  - Xue J
AD  - College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu Province, 
      China.
FAU - Xie, Mei-Lin
AU  - Xie ML
AUID- ORCID: 0000-0001-6066-6363
AD  - College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu Province, 
      China. xiemeilin@suda.edu.cn.
FAU - Xie, Tao
AU  - Xie T
AUID- ORCID: 0000-0001-9364-5083
AD  - Department of Neurosurgery, The Affiliated Suzhou Hospital of Nanjing Medical 
      University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 
      Suzhou, Jiangsu Province, China. xietao@njmu.edu.cn.
LA  - eng
GR  - NMUB2020254/Research Fund of Nanjing Medical University/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231114
PL  - Germany
TA  - Strahlenther Onkol
JT  - Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et 
      al]
JID - 8603469
RN  - 0 (Coumarins)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - XH1TI1759C (osthol)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - 0 (Radiation-Sensitizing Agents)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Coumarins/pharmacology
MH  - *TOR Serine-Threonine Kinases/metabolism
MH  - *Glycolysis/drug effects/radiation effects
MH  - *Glycogen Synthase Kinase 3 beta/metabolism
MH  - *Mice, Nude
MH  - Cell Line, Tumor
MH  - *AMP-Activated Protein Kinases/metabolism
MH  - *Radiation Tolerance/drug effects
MH  - *Signal Transduction/drug effects
MH  - Carcinoma, Hepatocellular/pathology/drug therapy
MH  - Liver Neoplasms/drug therapy
MH  - Male
MH  - Humans
MH  - Radiation-Sensitizing Agents/pharmacology
MH  - Mice, Inbred BALB C
OTO - NOTNLM
OT  - Glucose metabolism
OT  - Glycogen synthase kinase-3beta
OT  - Hepatic cancer
OT  - Natural product
OT  - Radiosensitization
EDAT- 2023/11/15 00:41
MHDA- 2024/04/23 16:23
CRDT- 2023/11/14 23:32
PHST- 2023/07/24 00:00 [received]
PHST- 2023/10/22 00:00 [accepted]
PHST- 2024/04/23 16:23 [medline]
PHST- 2023/11/15 00:41 [pubmed]
PHST- 2023/11/14 23:32 [entrez]
AID - 10.1007/s00066-023-02173-8 [pii]
AID - 10.1007/s00066-023-02173-8 [doi]
PST - ppublish
SO  - Strahlenther Onkol. 2024 May;200(5):444-452. doi: 10.1007/s00066-023-02173-8. 
      Epub 2023 Nov 14.