Unknown

Dataset Information

0

Apolipoprotein A-I mimetic peptide 4F suppresses tumor-associated macrophages and pancreatic cancer progression.


ABSTRACT: Pancreatic cancer is an aggressive malignancy that is unresponsive to conventional radiation and chemotherapy. Therefore, development of novel immune therapeutic strategies is urgently needed. L-4F, an Apolipoprotein A-I (ApoA-I) mimetic peptide, is engineered to mimic the anti-inflammatory and anti-oxidative functionalities of ApoA-I. In this work, H7 cells were orthotopically implanted in C57BL/6 mice and treated with L-4F. Then, pancreatic cancer progression and the inflammatory microenvironment were investigated in vivo. The cytotoxicity of L-4F toward H7 cells was assessed in vitro. Furthermore, we investigated the effects of L-4F on macrophage polarization by analyzing the polarization and genes of mouse bone marrow-derived macrophages in vitro. The results show that L-4F substantially reduced the tumorigenicity of H7 cells. L-4F inhibited inflammation by reducing the accumulation of inflammatory cells, such as IL-17A-, IL-4-, GM-CSF-, IL-1?-, and IL-6-producing cells and Th1 and Th17. Notably, L-4F also decreased the percentage of macrophages in tumor tissues, especially M2 macrophages (CD11b+F4/80+CD206+), which was also confirmed in vitro. Additionally, the expression of the M2 marker genes Arg1, MRC1, and CCL22 and the inflammatory genes IL-6, iNOS, and IL-12 was decreased by L-4F, indicating that L-4F prevents M2 type macrophage polarization. However, L-4F could not directly attenuate H7 cell invasion or proliferation and did not induce apoptosis. In addition, L-4F potently down-regulated STAT3, JNK and ERK signaling pathways but not affects the phosphorylation of p38 in RAW 264.7 cells. These results suggest that L-4F exhibits an effective therapeutic effect on pancreatic cancer progression by inhibiting tumor-associated macrophages and inflammation.

SUBMITTER: Peng M 

PROVIDER: S-EPMC5725125 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

Apolipoprotein A-I mimetic peptide 4F suppresses tumor-associated macrophages and pancreatic cancer progression.

Peng Meiyu M   Zhang Qi Q   Cheng Yingnan Y   Fu Shuyu S   Yang Huipeng H   Guo Xiangdong X   Zhang Jieyou J   Wang Lina L   Zhang Lijuan L   Xue Zhenyi Z   Li Yan Y   Da Yurong Y   Yao Zhi Z   Qiao Liang L   Zhang Rongxin R  

Oncotarget 20170922 59


Pancreatic cancer is an aggressive malignancy that is unresponsive to conventional radiation and chemotherapy. Therefore, development of novel immune therapeutic strategies is urgently needed. L-4F, an Apolipoprotein A-I (ApoA-I) mimetic peptide, is engineered to mimic the anti-inflammatory and anti-oxidative functionalities of ApoA-I. In this work, H7 cells were orthotopically implanted in C57BL/6 mice and treated with L-4F. Then, pancreatic cancer progression and the inflammatory microenvironm  ...[more]

Similar Datasets

| S-EPMC7204910 | biostudies-literature
| S-EPMC4432873 | biostudies-literature
2012-09-30 | E-GEOD-36933 | biostudies-arrayexpress
| S-EPMC4442877 | biostudies-literature
2012-09-30 | GSE36933 | GEO
| S-EPMC2889631 | biostudies-literature
| S-EPMC4083685 | biostudies-literature
| S-EPMC4194270 | biostudies-literature
| S-EPMC5706511 | biostudies-literature
| S-EPMC5975068 | biostudies-literature