Propofol inhibits pancreatic cancer progress under hypoxia via ADAM8

Abstract

Background To investigate the potential anti-tumoral properties of propofol in pancreatic cancer and elucidate the underlying mechanisms. Methods The relative expression of ADAM metallopeptidase domain 8 (ADAM8) in response to hypoxia in Panc1 cells was analyzed by western blotting. The enzymatic activity was determined by fluorescence release from PEPDAB013 decomposition. Cell growth was measured via cell counting and cell viability was measured using CCK-8 kit. Cell migrative capacity was evaluated by transwell and adhesion assay. The relative abundance of angiogenesis-related markers including platelet-derived growth factor AA, angiogenin, endothelin-1 and vascular endothelial growth factor were determined by real-time polymerase chain reaction and western blotting. The antitumoral activity of propofol was investigated with Panc1derived xenograft mice model. Results ADAM8 was significantly induced by hypoxia and efficiently inhibited by co-treatment with propofol. Propofol suppressed proliferation and compromised viability of Panc1 cells. In addition, the migrative capacity was greatly inhibited by propofol dosage. Comprehensive profiling of angiogenesis-related markers demonstrated that propofol remarkably suppressed neovascularization response in Panc1 cells under hypoxia. We further uncovered that propofol administration via subcutaneous injection delayed xenograft tumor progression. Conclusion Propofol specifically inhibited ADAM8 expression and activation in response to hypoxia in pancreatic cancer, and held great value for therapeutic effects.

Propofol suppresses hypoxia‐induced esophageal cancer cell migration, invasion, and EMT through regulating lncRNA TMPO‐AS1/miR‐498 axis

“…8 Gao et al demonstrated that propofol suppressed hypoxia-induced cell progression in pancreatic cancer. 26 Consistent with these data, our results indicated that propofol weakened the inhibitory effect of hypoxia on EC cell migration, invasion, and EMT through downregulating HIF-1α level. Therefore, propofol acted as a negative regulator in hypoxia-induced EC cell progression.…”

Propofol Regulates ADAM8 in Pancreatic Cancer Cells by Targeting SP1

“…A number of studies have indicated that propofol suppresses the malignancy of a variety of human cancers, such as hepatocellular carcinoma (HCC) [23] , breast cancer [24] , and lung cancer [25] . Moreover, some studies have suggested a possible correlation between propofol and chemotherapy, though the results are unde ned [26] .Previous studies conducted by our research group have shown that propofol inhibits pancreatic tumor growth via ADAM8 [10] and further found that propofol speci cally inhibited ADAM8 expression and activation in response to hypoxia in pancreatic cancer [11] . The results of present study are consistent with these previous reports.…”

“…Once upregulated, ADAM8 is proteolytically active and resultsin enhanced shedding of cell adhesion molecules, cytokine receptors and extracellular matrix (ECM) components [9] . In our previous study, we found that propofol could downregulate ADAM8 expression under hypoxic conditions [10] , which partially inhibits the activity of AMAD8 (this was not observed when compared with the control drug Batimastat, BB-94) [10,11] .For these reasons it is possible that other mechanisms participate in the effect of propofolon pancreatic cancer through ADAM8.…”

Comprehensive Analysis of Coding and Non-coding RNA Transcriptomes Related to Hypoxic Adaptation in Tibetan Chickens

“…For example, NGFR is the receptor of NGF, which can induce chick CAM neovascularization [46]. Studies have shown that ADAM8 is signi cantly induced by hypoxia and plays a role in the proliferation and migration of endothelial cells during angiogenesis [47,48]. Therefore, we speculate that the enhanced tolerance of Tibetan chicken embryo CAM under hypoxic conditions is ascribed to miRNA-mediated modulation of the related target mRNAs, further regulating HIF, which enables it to maintain hypoxic adaptation via the promotion of angiogenesis and blood circulation.…”