PMID- 36175804
OWN - NLM
STAT- MEDLINE
DCOM- 20221003
LR  - 20230120
IS  - 1559-131X (Electronic)
IS  - 1357-0560 (Linking)
VI  - 39
IP  - 12
DP  - 2022 Sep 29
TI  - The natural medicinal fungus Huaier promotes the anti-hepatoma efficacy of 
      sorafenib through the mammalian target of rapamycin-mediated autophagic cell 
      death.
PG  - 221
LID - 10.1007/s12032-022-01797-7 [doi]
AB  - Sorafenib (SOR) is currently the first line molecular targeting agent for 
      advanced liver cancer therapy. Unfortunately, the insensitivity of liver cancer 
      patients to SOR relatively limits its effectiveness. Huaier (HUA), a natural 
      medicinal parasitic fungus found on the Sophora japonica Linn., has been widely 
      employed as an adjuvant medication for numerous malignancies due to its potent 
      anti-tumoral properties. This study aims to elucidate the enhancing therapeutic 
      efficacy of HUA on SOR treatment in hepatocellular carcinoma (HCC) cells and 
      mouse models. The CCK-8, clone formation, flow cytometry, immunofluorescence, 
      transmission electron microscopy, western blot, bioinformatic analysis, and 
      xenograft tumor assays were performed to evaluate the synergistic anti-hepatoma 
      efficacy and mechanisms of HUA-SOR combination treatment on HCC cells. The 
      results revealed combination treatment further inhibited proliferation, promoted 
      apoptosis, enhanced autophagy of HCC cells, and suppressed the growth of 
      transplanted tumors in mice, compared with either HUA or SOR treatment alone. For 
      Hep3B and Huh7 cells, the optimal synergistic doses of HUA in combination with 
      SOR were 8 mg/mL + 4 muM and 4 mg/mL + 2 muM, with combination index values of 
      0.646 and 0.588, respectively. Additionally, the underlying mechanisms might be 
      related to biological processes that are mediated by mammalian target of 
      rapamycin (mTOR). The combination treatment downregulated the protein expression 
      levels of p-mTOR, p-p70S6K, p62, and upregulated the protein expression levels of 
      Beclin-1 and LC3B-II. The mTOR activator MHY1485 attenuated the effect of HUA-SOR 
      combination by inhibiting autophagy, suggesting HUA may potentiate the 
      sensitivity of HCC cells to SOR by partially inducing mTOR-mediated autophagic 
      cell death. These findings might provide a rationale experimental foundation for 
      clinical applications of HUA with SOR.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Zhang, Zhengguang
AU  - Zhang Z
AUID- ORCID: 0000-0003-1053-5570
AD  - School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese 
      Medicine, Nanjing, 210023, China. zhengguangzhang@njucm.edu.cn.
FAU - Shen, Cunsi
AU  - Shen C
AD  - Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, 
      Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210023, 
      China.
FAU - Zhou, Fuqiong
AU  - Zhou F
AD  - Central Laboratory, Nanjing Hospital of Chinese Medicine, Affiliated to Nanjing 
      University of Chinese Medicine, Nanjing, 210022, China. zhoufuqiong@njucm.edu.cn.
LA  - eng
GR  - 82004118/National Natural Science Foundation of China/
GR  - 81904029/National Natural Science Foundation of China/
GR  - NZY82004118/Natural Science Youth Foundation of Nanjing University of Chinese 
      Medicine/
GR  - NZY81904029/Natural Science Youth Foundation of Nanjing University of Chinese 
      Medicine/
GR  - Z2020015/Medical Scientific Research Project of Jiangsu Provincial Health 
      Commission/
GR  - JQX21010/Outstanding Youth Fund Project of Nanjing Health Science and Technology 
      Development/
GR  - NJSZYYQNRC-2020-ZFQ/Traditional Chinese Medicine Youth Talent Training Program of 
      Nanjing/
PT  - Journal Article
DEP - 20220929
PL  - United States
TA  - Med Oncol
JT  - Medical oncology (Northwood, London, England)
JID - 9435512
RN  - 0 (Beclin-1)
RN  - 0 (Complex Mixtures)
RN  - 0 (huaier)
RN  - 9ZOQ3TZI87 (Sorafenib)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - M03GIQ7Z6P (Sincalide)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
EIN - Med Oncol. 2023 Jan 21;40(2):83. PMID: 36670337
MH  - Animals
MH  - *Autophagic Cell Death
MH  - Beclin-1
MH  - *Carcinoma, Hepatocellular/drug therapy
MH  - Complex Mixtures
MH  - Fungi
MH  - Humans
MH  - *Liver Neoplasms/drug therapy
MH  - Mammals
MH  - Mice
MH  - Ribosomal Protein S6 Kinases, 70-kDa
MH  - Sincalide
MH  - Sirolimus
MH  - Sorafenib/pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Trametes
OTO - NOTNLM
OT  - Autophagic cell death
OT  - Hepatocellular carcinoma
OT  - Huaier
OT  - Sorafenib
EDAT- 2022/09/30 06:00
MHDA- 2022/10/04 06:00
CRDT- 2022/09/29 23:41
PHST- 2022/04/28 00:00 [received]
PHST- 2022/07/15 00:00 [accepted]
PHST- 2022/09/29 23:41 [entrez]
PHST- 2022/09/30 06:00 [pubmed]
PHST- 2022/10/04 06:00 [medline]
AID - 10.1007/s12032-022-01797-7 [pii]
AID - 10.1007/s12032-022-01797-7 [doi]
PST - epublish
SO  - Med Oncol. 2022 Sep 29;39(12):221. doi: 10.1007/s12032-022-01797-7.