PMID- 28472762
OWN - NLM
STAT- MEDLINE
DCOM- 20180423
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 30
DP  - 2017 Jul 25
TI  - Oroxylin A inhibits the generation of Tregs in non-small cell lung cancer.
PG  - 49395-49408
LID - 10.18632/oncotarget.17218 [doi]
AB  - Oroxylin A (OA), a naturally occurring monoflavonoid isolated from Scutellariae 
      radix, has previously been reported to inhibit the proliferation of several 
      cancer cell lines. CD4+CD25+Foxp3+ regulatory T cells (Tregs) play an important 
      role in maintenance of immunologic self-tolerance. Tregs also increase in cancer 
      and take part in suppressing antitumor immune responses. Here, we explored how OA 
      affected the Tregs in lung cancer environment and the involved underlying 
      mechanism. It is found that OA reversed the generation of Tregs induced by H460 
      lung cancer cells co-culture. Furthermore, in vivo, OA reduced tumor formation 
      rate and attenuated Foxp3 expression in tumor-infiltrating lymphocytes. We also 
      found that transforming growth factor-beta1 (TGF-beta1) neutralizing antibody reversed 
      the enhancement of Treg number and expression of p-Smad3'p-p38'p-JNK'p-ERK1/2 in 
      the co-culture model. Moreover, OA reduced the secretion of TGF-beta1 and 
      down-regulated the activation of NF-kappaB signaling in H460 cells. OA also inhibited 
      Treg activity by a direct inhibition of the T cells' response to TGF-beta1. In 
      conclusion, our study demonstrated that OA inhibits the generation of Tregs in 
      lung cancer environment by inhibiting the T cells' response to TGF-beta1 and 
      decreasing the secretion of TGF-beta1 in lung cancer cells via NF-kappaB signaling.
FAU - Shen, Le
AU  - Shen L
AD  - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of 
      Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, 
      China Pharmaceutical University, Nanjing 210009, People's Republic of China.
FAU - Zhang, Lu-Lu
AU  - Zhang LL
AD  - Department of Toxicology, The Key Laboratory of Modern Toxicology of Ministry of 
      Education, School of Public Health, Nanjing Medical University, Nanjing 211166, 
      People's Republic of China.
FAU - Li, Hui
AU  - Li H
AD  - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of 
      Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, 
      China Pharmaceutical University, Nanjing 210009, People's Republic of China.
FAU - Liu, Xiao
AU  - Liu X
AD  - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of 
      Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, 
      China Pharmaceutical University, Nanjing 210009, People's Republic of China.
FAU - Yu, Xiao-Xuan
AU  - Yu XX
AD  - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of 
      Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, 
      China Pharmaceutical University, Nanjing 210009, People's Republic of China.
FAU - Hu, Po
AU  - Hu P
AD  - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of 
      Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, 
      China Pharmaceutical University, Nanjing 210009, People's Republic of China.
FAU - Hui, Hui
AU  - Hui H
AD  - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of 
      Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, 
      China Pharmaceutical University, Nanjing 210009, People's Republic of China.
FAU - Guo, Qing-Long
AU  - Guo QL
AD  - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of 
      Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, 
      China Pharmaceutical University, Nanjing 210009, People's Republic of China.
FAU - Zhang, Shuai
AU  - Zhang S
AD  - Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer 
      Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, 
      Cancer Institute of Jiangsu Province, Nanjing 210009, People's Republic of China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Biomarkers)
RN  - 0 (Flavonoids)
RN  - 0 (NF-kappa B)
RN  - 0 (Transforming Growth Factor beta)
RN  - 53K24Z586G (5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one)
SB  - IM
MH  - Animals
MH  - Biomarkers
MH  - Carcinoma, Non-Small-Cell Lung/*immunology/metabolism
MH  - Cell Line, Tumor
MH  - Coculture Techniques
MH  - Disease Models, Animal
MH  - Flavonoids/*pharmacology
MH  - Humans
MH  - Immunophenotyping
MH  - Jurkat Cells
MH  - Leukocytes, Mononuclear/drug effects/immunology/metabolism
MH  - Lung Neoplasms/*immunology/metabolism
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - Signal Transduction/drug effects
MH  - T-Lymphocytes, Regulatory/cytology/*drug effects/*immunology/metabolism
MH  - Transforming Growth Factor beta/metabolism
MH  - Xenograft Model Antitumor Assays
PMC - PMC5564777
OTO - NOTNLM
OT  - NF-kappaB
OT  - TGF-beta1
OT  - Tregs
OT  - oroxylin A
COIS- CONFLICTS OF INTEREST The authors declare that they have no competing interests.
EDAT- 2017/05/05 06:00
MHDA- 2018/04/24 06:00
PMCR- 2017/07/25
CRDT- 2017/05/05 06:00
PHST- 2017/01/23 00:00 [received]
PHST- 2017/03/22 00:00 [accepted]
PHST- 2017/05/05 06:00 [pubmed]
PHST- 2018/04/24 06:00 [medline]
PHST- 2017/05/05 06:00 [entrez]
PHST- 2017/07/25 00:00 [pmc-release]
AID - 17218 [pii]
AID - 10.18632/oncotarget.17218 [doi]
PST - ppublish
SO  - Oncotarget. 2017 Jul 25;8(30):49395-49408. doi: 10.18632/oncotarget.17218.