PMID- 35400284
OWN - NLM
STAT- MEDLINE
DCOM- 20220412
LR  - 20221207
IS  - 2165-5987 (Electronic)
IS  - 2165-5979 (Print)
IS  - 2165-5979 (Linking)
VI  - 13
IP  - 4
DP  - 2022 Apr
TI  - Matrine Combined with Mammalian Target of Rapamycin Inhibitor Enhances Anti-Tumor 
      Efficacy of dendritic cell Vaccines in hepatocellular carcinoma.
PG  - 9274-9283
LID - 10.1080/21655979.2022.2037855 [doi]
AB  - Dendritic cells (DCs), as the most important antigen-presenting cells, play a 
      crucial role in T cell activation. The latest research showed that inhibition of 
      the mammalian target of rapamycin (mTOR) could enhance DCs maturation, promoting 
      antigen presentation. Matrine has been identified as one of the key alkaloids 
      isolated from the roots of Sophora flavescens. In present study, we combined 
      matrine and mTOR inhibitor KU0063794 to observe the DCs functions, especially the 
      antigen presentation ability. DCs were activated by phosphate-buffered saline 
      (PBS), lipopolysaccharide (LPS), LPS+KU0063794, LPS+Matrine, and 
      LPS+KU0063794+Matrine. The surface markers in DCs, proliferation of T cells and 
      cytokines were detected by flow cytometry, cell counting kit-8 (CCK-8) and 
      enzyme-linked immunosorbent assay (ELISA), respectively. The lactate 
      dehydrogenase (LDH) release test was used to detect the antitumor efficacy. The 
      tumor growth curves were plotted by calculating tumor volume. The apoptosis was 
      detected by Terminal-deoxynucleoitidyl Transferase-Mediated Nick End Labeling 
      (TUNEL) method. Matrine combined with KU0063794 could enhance the maturity of 
      DCs, T cells proliferation and cytokines secretion (P < 0.05). The cytotoxic T 
      lymphocytes (CTL) killing efficacy of LPS+KU0063794+Matrine group was higher than 
      other groups (P < 0.05). In vivo, the tumor weights and volumes in 
      LPS+KU0063794+Matrine group were lower than other groups. The detections of tumor 
      apoptosis were increased in LPS+KU0063794+Matrine group (P < 0.05). DC vaccine 
      with mTOR inhibitor and matrine could significantly improve the efficacy of 
      antitumor immunity in vitro and vivo. These findings illustrated that mTOR 
      inhibitor and matrine, as two immunomodulators, could enhance DC activation and 
      differentiation.
FAU - Zhou, Ning
AU  - Zhou N
AD  - Department of Gastroenterology, The First People's Hospital of Lanzhou City, 
      Lanzhou Gansu, China.
AD  - Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou Gansu, 
      China.
FAU - Li, Sheng
AU  - Li S
AD  - Department of Gastroenterology, The First People's Hospital of Lanzhou City, 
      Lanzhou Gansu, China.
FAU - Zhang, Fan
AU  - Zhang F
AD  - Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou Gansu, 
      China.
FAU - Chen, Cong
AU  - Chen C
AD  - Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou Gansu, 
      China.
FAU - Li, Yumin
AU  - Li Y
AD  - Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou Gansu, 
      China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Bioengineered
JT  - Bioengineered
JID - 101581063
RN  - 0 (Alkaloids)
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Quinolizines)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
RN  - 0 (Matrines)
SB  - IM
MH  - *Alkaloids/pharmacology
MH  - *Carcinoma, Hepatocellular/drug therapy/pathology
MH  - Cytokines
MH  - Dendritic Cells
MH  - Humans
MH  - Lipopolysaccharides
MH  - *Liver Neoplasms/drug therapy/pathology
MH  - Quinolizines
MH  - Sirolimus
MH  - TOR Serine-Threonine Kinases
MH  - Matrines
PMC - PMC9161910
OTO - NOTNLM
OT  - CTL
OT  - Huh7 cells
OT  - Matrine
OT  - dendritic cells
OT  - mTOR inhibitor
OT  - nude mice
OT  - vaccine
COIS- No potential conflict of interest was reported by the authors.
EDAT- 2022/04/12 06:00
MHDA- 2022/04/13 06:00
PMCR- 2022/04/10
CRDT- 2022/04/11 05:23
PHST- 2022/04/11 05:23 [entrez]
PHST- 2022/04/12 06:00 [pubmed]
PHST- 2022/04/13 06:00 [medline]
PHST- 2022/04/10 00:00 [pmc-release]
AID - 2037855 [pii]
AID - 10.1080/21655979.2022.2037855 [doi]
PST - ppublish
SO  - Bioengineered. 2022 Apr;13(4):9274-9283. doi: 10.1080/21655979.2022.2037855.