PMID- 30968715
OWN - NLM
STAT- MEDLINE
DCOM- 20190729
LR  - 20200225
IS  - 2058-7384 (Electronic)
IS  - 0394-6320 (Print)
IS  - 0394-6320 (Linking)
VI  - 33
DP  - 2019 Jan-Dec
TI  - PCC0208018 exerts antitumor effects by activating effector T cells.
PG  - 2058738419843366
LID - 10.1177/2058738419843366 [doi]
LID - 2058738419843366
AB  - Poor prognosis is associated with melanoma due to immunosuppression profiles, 
      suggesting that immune alterations have an important role in the occurrence, 
      growth, and metastasis of melanoma. Here, we found that PCC0208018, a 
      small-molecule compound, enhanced T cell proliferation and activation to release 
      interferon gamma (IFN-gamma) and interleukin-2 (IL-2) without blocking the programmed 
      cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) binding and did not 
      directly affect tumor cell viability in vitro. Furthermore, PCC0208018 increased 
      the phosphorylation of protein kinase B (PKB/AKT) as well as extracellular 
      regulated protein kinases (ERK) in human peripheral blood mononuclear cells 
      (PBMCs) in vitro. The secretion of cytokines induced by PCC0208018 was 
      significantly suppressed by the PI3K inhibitor GDC-0941. In B16-F10 
      melanoma-harboring mice, PCC0208018 significantly inhibited tumor growth as well 
      as increasing CD3(+), CD3(+)CD4(+), and CD3(+)CD8(+) T cell abundance in tumors 
      without affecting PD-L1 expression. This study showed that PCC0208018 potentially 
      increased PBMCs proliferation and function by activating the phosphatidylinositol 
      3 kinase (PI3K)/AKT and mitogen-activated protein kinase (MEK)/ERK pathways to 
      exert antitumor effects.
FAU - Ge, Minmin
AU  - Ge M
AD  - 1 School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug 
      Evaluation (Yantai University), Ministry of Education, Collaborative Innovation 
      Center of Advanced Drug Delivery System and Biotech Drugs in Universities of 
      Shandong, Yantai University, Yantai, China.
FAU - Hu, Zhengping
AU  - Hu Z
AD  - 2 School of Public Health and Management, Institute of Toxicology, Binzhou 
      Medical University, Yantai, China.
FAU - Chen, Xiao
AU  - Chen X
AUID- ORCID: 0000-0003-4506-0544
AD  - 1 School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug 
      Evaluation (Yantai University), Ministry of Education, Collaborative Innovation 
      Center of Advanced Drug Delivery System and Biotech Drugs in Universities of 
      Shandong, Yantai University, Yantai, China.
FAU - Du, Guangying
AU  - Du G
AD  - 1 School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug 
      Evaluation (Yantai University), Ministry of Education, Collaborative Innovation 
      Center of Advanced Drug Delivery System and Biotech Drugs in Universities of 
      Shandong, Yantai University, Yantai, China.
FAU - Wang, Hongbo
AU  - Wang H
AD  - 1 School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug 
      Evaluation (Yantai University), Ministry of Education, Collaborative Innovation 
      Center of Advanced Drug Delivery System and Biotech Drugs in Universities of 
      Shandong, Yantai University, Yantai, China.
FAU - Liu, Rumeng
AU  - Liu R
AD  - 1 School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug 
      Evaluation (Yantai University), Ministry of Education, Collaborative Innovation 
      Center of Advanced Drug Delivery System and Biotech Drugs in Universities of 
      Shandong, Yantai University, Yantai, China.
FAU - Ye, Liang
AU  - Ye L
AD  - 2 School of Public Health and Management, Institute of Toxicology, Binzhou 
      Medical University, Yantai, China.
FAU - Tian, Jingwei
AU  - Tian J
AUID- ORCID: 0000-0002-3877-0903
AD  - 1 School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug 
      Evaluation (Yantai University), Ministry of Education, Collaborative Innovation 
      Center of Advanced Drug Delivery System and Biotech Drugs in Universities of 
      Shandong, Yantai University, Yantai, China.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Int J Immunopathol Pharmacol
JT  - International journal of immunopathology and pharmacology
JID - 8911335
RN  - 0 (Antineoplastic Agents)
MH  - Animals
MH  - Antineoplastic Agents/chemistry/*pharmacology/therapeutic use
MH  - CHO Cells
MH  - Cell Proliferation/drug effects/physiology
MH  - Cells, Cultured
MH  - Cricetinae
MH  - Cricetulus
MH  - Humans
MH  - Male
MH  - Melanoma, Experimental/drug therapy/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Skin Neoplasms/drug therapy/*metabolism
MH  - T-Lymphocytes/*metabolism
MH  - Xenograft Model Antitumor Assays
PMC - PMC6458668
OTO - NOTNLM
OT  - PCC0208018
OT  - PI3K/AKT pathway
OT  - cancer immunotherapy
OT  - melanoma
COIS- Declaration of conflicting interests: The author(s) declared no potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article.
EDAT- 2019/04/11 06:00
MHDA- 2019/07/30 06:00
PMCR- 2019/04/10
CRDT- 2019/04/11 06:00
PHST- 2019/04/11 06:00 [entrez]
PHST- 2019/04/11 06:00 [pubmed]
PHST- 2019/07/30 06:00 [medline]
PHST- 2019/04/10 00:00 [pmc-release]
AID - 10.1177_2058738419843366 [pii]
AID - 10.1177/2058738419843366 [doi]
PST - ppublish
SO  - Int J Immunopathol Pharmacol. 2019 Jan-Dec;33:2058738419843366. doi: 
      10.1177/2058738419843366.