Lipoxin A4 Supresses Prostate Cancer Cells Via Blocking the Activation of Macrophages
|School||Huazhong University of Science and Technology|
|Course||Pathology and Pathophysiology|
|Keywords||LXA4 inflammation resolution macrophages prostate cancer cells|
Background: Tumor-associated macrophages play a key role in tumor progression, but whether they have a tumor-progressive effect remains controversial. In the past decade, tumor-associated macrophages (TAMs) have been proposed as a major contributor to tumor progression. Nevertheless, the interaction between TAMs and cancer cells is very complicated and has not been clearly clarified. Most importantly, whether TAMs increase tumor-progression remains a controversial subject. For example,an elevated levels of TAMs is associated with a better prognosis in lung cancer , but with a poor prognosis in breast cancer. Today,it’s been identified that the in?ammatory microenvironment plays a importent role in the progression of solid malignant tumors,and then macrophages will be activated into TAMS. It was confirmed that it was reported non-steroidal anti-in?ammatory drugs (NSAIDs) suppressed the proliferation, induced the apoptosis . As the first family of endogenous“braking signals”in inflammation identified in vivo, LXA4 is a one of novel NSAIDs. This article takes a research in the effects of TAMS to prostate cancer,and the effects of LXA4 which is a kind of human endogenous substances in the progression of PC-3.Objective: To investigate the impact of activated macrophages to the migration, adhesion and proliferation in prostate cancer cells (PC-3) from the cellular level, and the effects of LXA4 on inhibiting the tumor progression.Methods: The PC-3 human prostate cancer cell line, RAW264.7 murine macrophage cell line, U937 human monocyte cell line and THP-1 human monocyte cell line were cultured in vitro and the experiment was divided into three groups: PC-3 cells cultured with control macrophage-conditioned media(CCM) as control group; added activated macrophage-conditioned media(AMCM) to the PC-3 cells as the injury group; add 200nmol/L LXA4 to the induced injury group as the agents intervention group .We took a research in their morphology ; cultured the PC-3 cells in vitro to cover the entire six-well plates, and drew a straight line with tips in the Center of each plate before add the supernatant to the plate, then observed the effects to the tumor cells; Similarly, cultured cells were divided into three groups in vitro, immunofluorescence was used to detect the expression of C23,NS, E-cadherin andβ-catenin;detected the expression of the genes and proteins of C23 and NS respectively by RT-PCR and Western Blot; examined the protein expression of NF-κB by Western Blot.Results: The morphological change implied weakening of cell adhesion and increasing of cell migration; the expression of C23,NS and NF-κB in the AMCM-treated cultures was distinctly higher than the control macrophage-conditioned media(CCM) group; tumor-associated macrophage activation downregulateed the expression of E-cadherin andβ-catenin; LXA4 inhibited C23,NS and NF-κB production and up-regulated the the expression of E-cadherin andβ-catenin.Conclusions: LXA4 effectively suppressed prostate cancer cells, LXA4 could be be an effective drug target for prostatic cancer therapy by blocking the activation of macrophages. The mechanisms may be that LXA4 downregulate the expression of NF-κB.