In order to investigate how macrophages promote lipid droplet hoarding in hepatocellular carcinoma cells and to delve into the roles of key metabolic enzymes of lipid droplets in the malignant biology of hepatocellular carcinoma cells, the present study was conducted to induce the generation of Hepa1-6 lipid droplets (LDs) using supernatants from tumor-associated macrophages (TAMs), and found that interleukin-10 (IL-10) in TAMs was found to promote the accumulation of lipid droplets. Acetyl-CoA carboxylase alpha (ACC1) is one of the key enzymes for fatty acid synthesis and influences the development of hepatocellular carcinoma. In this study, ACC1 was found to be highly expressed in LDhigh Hepa1-6, and subsequent blockade of ACC1 activity by means of a small molecule inhibitor of ACC1, siRNA interference, and CRISPR-cas9 knockdown was found to reduce the accumulation of Hepa1-6 lipid droplets, as well as to reduce the malignant biological behavior of Hepa1-6 proliferation, and to promote the occurrence of apoptotic events. In summary, IL-10 released by TAMs promoted lipid droplet formation in hepatocellular carcinoma cells, leading to malignant proliferation and apoptosis of hepatocellular carcinoma cells. ACC1 plays a key role in the promotion of lipid droplet accumulation in hepatocellular carcinoma cells by TAMs and may be regulated by IL-10 released by TAMs, and these findings may provide a new target for hepatocellular carcinoma treatment.

Currently the main treatment of acute myeloid leukemia (AML) is chemotherapy combining hematopoietic stem cell transplantation. However, the unbearable side effect of chemotherapy and the high risk of life-threatening infections and disease relapse following hematopoietic stem cell transplantation restrict its application in clinical practice. Thus, there is an urgent need to develop alternative therapeutic tactics with significant efficacy and attenuated adverse effects. Here, we revealed that umbilical cord-derived mesenchymal stem cells (UC-MSC) efficiently induced AML cell differentiation by shuttling the neutrophil elastase (NE)-packaged extracellular vesicles (EVs) into AML cells. Interestingly, the generation and release of NE-packaged EVs could be dramatically increased by vitamin D receptor (VDR) activation in UC-MSC. Chemical activation of VDR by using its agonist 1α,25-dihydroxyvitamin D3 efficiently enhanced the pro-differentiation capacity of UC-MSC and then alleviated malignant burden in AML mouse model. Based on these discoveries, to evade the risk of hypercalcemia, we synthetized and identified sw-22, a novel non-steroidal VDR agonist, which exerted a synergistic pro-differentiation function with UC-MSC on mitigating the progress of AML. Collectively, our findings provided a non-gene editing MSC-based therapeutic regimen to overcome the differentiation blockade in AML.