Abstract:Objective: To investigate the effect of pinocembrin (Pin) on the malignant progression of esophageal squamous carcinoma cells and its regulatory mechanism on the Janus activated kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway.Methods: Human esophageal squamous carcinoma cell line KYSE-410 was randomly separated into KYSE-410 group, Pin-low concentration (Pin-L) group, Pin-medium concentration (Pin-M) group, Pin-high concentration (Pin-H) group, and Pin-H+JAK2 activator (Pin-H+Broussonin E) group. CCK-8 method and clone plate assay were applied to detect the proliferative activity of cells in each group. Transwell experiment was applied to detect the migration and invasion abilities of cells; flow cytometry was applied to detect the apoptosis of cells in each group; Western blot was applied to detect the expression levels of JAK2/STAT3 signaling pathway related proteins of cells in each group. Results: Compared with the KYSE-410 group, the cell survival rates (79.91±2.31, 62.33±1.41, 51.17±1.05, F=307.400), the number of clone cells formed (162.82±6.33, 144.59± 5.09, 120.18±3.72, F=209.800), and the number of migrated cells (77.73±3.26, 60.83±2.41, 49.28±1.60, F=360.314) were observed in the Pin-L, Pin-M, and Pin-H groups. The number of invasive cells (62.72±2.42, 50.93±2.07, 32.47±1.55, F=460.221), as well as p-JAK2/JAK2 (0.77±0.06, 0.60±0.04, 0.42±0.03, F=68.226) and p-STAT3/STAT3 values (0.70±0.06, 0.58±0.04, 0.39±0.03, F=61.160) in the cells, decreased (P<0.001), while the apoptosis rate (24.72±2.18, 39.62±3.66, 48.33±4.13, F=235.11) increased (P<0.001), the addition of Broussonin E reversed the inhibitory effect of Pin on the malignant progression of KYSE-410 cells (P<0.05). Conclusion: Pin can inhibit the malignant progression of esophageal squamous carcinoma cells, and its mechanism of action may be related to the inhibition of the JAK2/STAT3 signaling pathway.
[1] Sung H,Ferlay J,Siegel R L,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer Clin,2021,71(3):209-249. [2] 刘冰,方存明,马小林.乔松素通过调节HIF-1α/BNIP3信号通路介导细胞自噬减轻缺氧/复氧诱导的心肌细胞损伤[J].河北医学,2022,28(11):1761-1768. [3] Li X,Zhai Y,Xi B,et al.Pinocembrin ameliorates skin Fibrosis via inhibiting TGF-β1 signaling pathway[J].Biomolecules,2021,11(8):1240-1241. [4] Gong H.Pinocembrin suppresses proliferation and enhances apoptosis in lung cancer cells in vitro by restraining autophagy[J].Bioengineered,2021,12(1):6035-6044. [5] 邹旺辉,钱楠楠,张萌,等.间充质干细胞临床前研究启示:间充质干细胞的细胞功能与JAK/STAT信号通路的关系[J].中国组织工程研究,2022,26(19):3192-3199. [6] 蒋可心,李宁,张旭.钙激活的氯离子通道A4通过抑制JAK激酶2/信号转导及转录激活蛋白3信号通路对食管癌细胞增殖、迁移及侵袭的影响[J].安徽医药,2021,25(3):474-478. [7] Huang S P,Guan X,Kai G Y,et al.Broussonin E suppresses LPS-induced inflammatory response in macrophages via inhibiting MAPK pathway and enhancing JAK2-STAT3 pathway[J].Chin Nat Med,2019,17(5):372-380. [8] Watanabe M,Otake R,Kozuki R,et al.Recent progress in multidisciplinary treatment for patients with esophageal cancer[J].Surg Today,2020,50(1):12-20. [9] Gu J,Huang H,Liu C,et al.Pinocembrin inhibited cardiomyocyte pyroptosis against doxorubicin-induced cardiac dysfunction via regulating Nrf2/Sirt3 signaling pathway[J].Int Immunopharmacol,2021,95(1):1-9. [10] Gao J,Lin S,Gao Y,et al.Pinocembrin inhibits the proliferation and migration and promotes the apoptosis of ovarian cancer cells through down-regulating the miRNA levels of N-cadherin and GABAB receptor[J].Biomed Pharmacother,2019,120(1):109505-109515. [11] 李毅,李文忠,师路,等.番泻苷B对胃癌细胞生长,凋亡,干样特性以及IL-6/JAK2/STAT3通路的影响[J].免疫学杂志,2021,37(10):861-867. [12] 张伟,于鸣,李伟,等.白皮杉醇调节JAK2/STAT3信号通路对胆囊癌细胞恶性生物学行为的影响[J].河北医药,2023,45(14):2090-2094. [13] 殷星,侯永超,杨利姣.基于JAK2/STAT3信号通路研究银杏内酯B对食管癌细胞增殖及糖酵解水平的影响[J].现代消化及介入诊疗,2023,28(4):442-446.