PMID- 31578578
OWN - NLM
STAT- MEDLINE
DCOM- 20200403
LR  - 20200403
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 42
IP  - 6
DP  - 2019 Dec
TI  - The prednisolone phosphate‑induced suppression of the angiogenic function of 
      tumor‑associated macrophages enhances the antitumor effects of doxorubicin on 
      B16.F10 murine melanoma cells in vitro.
PG  - 2694-2705
LID - 10.3892/or.2019.7346 [doi]
AB  - Several lines of evidence have clearly demonstrated the role of the tumor 
      microenvironment in favoring the drug resistance of melanoma cells, as well as 
      the progression of this cancer type. Since our previous studies proved that the 
      accumulation of prednisolone disodium phosphate (PLP) in melanoma tissue 
      inhibited tumor growth by exerting anti‑angiogenic effects on the most abundant 
      cells of the tumor microenvironment, tumor‑associated macrophages (TAMs), the 
      present study investigated whether PLP could enhance the cytotoxic effects of 
      doxorubicin (DOX) on B16.F10 murine melanoma cells. To assess the antitumor 
      efficacy of the combined therapeutic approach based on PLP and DOX, we used a 
      co‑culture system composed of bone marrow‑derived macrophages (BMDMs) and B16.F10 
      murine melanoma cells at a cell density ratio that approximates the melanoma 
      microenvironment in vivo, ensuring the polarization of the BMDMs into TAMs. Thus, 
      we assessed the combined therapeutic effects of PLP and DOX on melanoma cell 
      proliferation and apoptosis, as well as on supportive processes for tumor growth, 
      such as oxidative stress as well as the angiogenic and inflammatory capacity of 
      the cell co‑culture. Our data demonstrated that the cytotoxicity of DOX was 
      potentiated mainly via the anti‑angiogenic activity of PLP in the melanoma 
      microenvironment in vitro. Moreover, the amplitude of the cytotoxicity of the 
      combined treatments may be linked to the degree of the suppression of the 
      pro‑angiogenic function of TAMs. Thus, the potent decrease in the expression of 
      the majority of the angiogenic and inflammatory proteins in TAMs following the 
      concomitant administration of PLP and DOX may be associated with their 
      anti‑proliferative, as well as pro‑apoptotic effects on B16.F10 melanoma cells. 
      However, the combination therapy tested did not affect the immunosuppressive 
      phenotype of the TAMs, as the levels of two important markers of the M2‑like 
      phenotype of macrophages (IL‑10 and Arg‑1) were not reduced or even increased 
      following these treatments. On the whole, the findings of this study indicated 
      that PLP improved the therapeutic outcome of DOX in the melanoma microenvironment 
      via the inhibition of the pro‑angiogenic function of TAMs.
FAU - Licarete, Emilia
AU  - Licarete E
AD  - Department of Molecular Biology and Biotechnology, Faculty of Biology and 
      Geology, Babes‑Bolyai University, 400006 Cluj‑Napoca, Romania.
FAU - Rauca, Valentin Florian
AU  - Rauca VF
AD  - Department of Molecular Biology and Biotechnology, Faculty of Biology and 
      Geology, Babes‑Bolyai University, 400006 Cluj‑Napoca, Romania.
FAU - Luput, Lavinia
AU  - Luput L
AD  - Department of Molecular Biology and Biotechnology, Faculty of Biology and 
      Geology, Babes‑Bolyai University, 400006 Cluj‑Napoca, Romania.
FAU - Patras, Laura
AU  - Patras L
AD  - Department of Molecular Biology and Biotechnology, Faculty of Biology and 
      Geology, Babes‑Bolyai University, 400006 Cluj‑Napoca, Romania.
FAU - Sesarman, Alina
AU  - Sesarman A
AD  - Department of Molecular Biology and Biotechnology, Faculty of Biology and 
      Geology, Babes‑Bolyai University, 400006 Cluj‑Napoca, Romania.
FAU - Banciu, Manuela
AU  - Banciu M
AD  - Department of Molecular Biology and Biotechnology, Faculty of Biology and 
      Geology, Babes‑Bolyai University, 400006 Cluj‑Napoca, Romania.
LA  - eng
PT  - Journal Article
DEP - 20191001
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Liposomes)
RN  - 752SY38R6C (prednisolone phosphate)
RN  - 80168379AG (Doxorubicin)
RN  - 9PHQ9Y1OLM (Prednisolone)
SB  - IM
MH  - Angiogenesis Inhibitors/pharmacology
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Doxorubicin/*pharmacology
MH  - Drug Delivery Systems
MH  - Humans
MH  - Liposomes/pharmacology
MH  - Macrophages/drug effects/pathology
MH  - Melanoma, Experimental/*drug therapy/pathology
MH  - Mice
MH  - Neovascularization, Pathologic/*drug therapy/pathology
MH  - Prednisolone/*analogs & derivatives/pharmacology
MH  - Tumor Microenvironment/drug effects
EDAT- 2019/10/04 06:00
MHDA- 2020/04/04 06:00
CRDT- 2019/10/04 06:00
PHST- 2019/02/14 00:00 [received]
PHST- 2019/08/20 00:00 [accepted]
PHST- 2019/10/04 06:00 [pubmed]
PHST- 2020/04/04 06:00 [medline]
PHST- 2019/10/04 06:00 [entrez]
AID - 10.3892/or.2019.7346 [doi]
PST - ppublish
SO  - Oncol Rep. 2019 Dec;42(6):2694-2705. doi: 10.3892/or.2019.7346. Epub 2019 Oct 1.