| 李丹阳,余明月,刘翠.车叶草苷酸对胰腺癌免疫逃逸的影响及调节机制[J].安徽医药,2025,29(7):1308-1314. |
| 车叶草苷酸对胰腺癌免疫逃逸的影响及调节机制 |
| Effect of asperulosidic acid on immune escape of pancreatic cancer and its regulatory mechanism |
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| DOI：10.3969/j.issn.1009-6469.2025.07.009 |
| 中文关键词: 胰腺肿瘤 车叶草苷酸 SW1990人胰腺癌细胞 Capan-1人胰腺癌细胞 环磷酸鸟苷 -磷酸腺苷合酶 -干扰素基因刺激因子(cGAS-STING)通路 免疫逃逸 调节机制 |
| 英文关键词: Pancreatic neoplasms Asperuloside acid SW1990 human pancreatic cancer cells Capan-1 human pancreatic can-cer cell cGAS-STING signal pathway Immune escape Regulatory mechanism |
| 基金项目:河北省中医药科研项目( 2021362) |
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| 中文摘要: |
| 目的探讨车叶草苷酸( ASPA)对胰腺癌免疫逃逸的影响及调节机制。方法该研究于 2023年 2—8月进行，对人胰腺导管上皮细胞( HPDE)与胰腺癌细胞( SW1990和 Capan-1)给予不同浓度的车叶草苷酸进行干预。建立小鼠异体移植瘤模型。按照细胞计数试剂盒( CCK-8)法检测细胞活力。 5-乙炔基 -2'-脱氧尿苷( EdU)染色法检测细胞增殖。流式细胞术检测细胞凋亡与 CD4+和 CD4+CD25+Foxp3+ Treg的水平。 Transwell试验检测细胞迁移与侵袭。蛋白质印迹法测定相关蛋白水平。酶联免疫吸附分析检测小鼠外周血转化生长因子 β1(TGF-β1)与白细胞介素 10(IL-10)水平。结果 ASPA处理前， SW1990和 Capan1的细胞活力分别为( 99.00±0.92)%、(99.00±0.87)%，200 mg/L的车叶草苷酸处理后 SW1990和 Capan-1细胞的活力分别降低至(38±1.63)%和( 42.67±1.58)%，差异有统计学意义( P<0.01)。车叶草苷酸抑制胰腺癌细胞增殖、迁移与侵袭，并显著促进凋亡(P<0.05)ASPA处理前， SW1990和 Capan-1增殖细胞数量( 42.67±4.56)个和( 46±4.55)个、凋亡细胞所占百分比( 5.3±1.10)%和(5.22±0.76%，ASPV处理后，增殖细胞数量明显降低至( 22±2.45)个和( 25.67±2.59)个，凋亡细胞所占百分比明显升高至(16.41±0.78)%和( 15.13±1.04)%。与对照组小鼠肿瘤体积( 845±95.96)mm3和肿瘤质量( 0.86±0.08)g相比，车叶草苷酸显著抑制了小鼠体内胰腺癌肿瘤的生长( P<0.05)肿瘤体积降至( 520.67±80.87)mm3肿瘤质量降至( 0.53±0.07)g。车叶草苷酸在胰腺癌中激活了cGAS-STING通路(P<0.05)。车叶草苷酸处理使正常胰腺癌小鼠外周血中 TGF-β1、IL-10和 CD4+的含量( 37.22±3.26)ng/L、(153.65±6.09)ng/L和( 43.27±5.62)ng/L降低至( 25.77±2.31)ng/L、(123.36±2.72)ng/L和( 32.47±3.21)ng/L， CD4+CD25+Foxp3+ Treg的含量从( 2.40±0.36)ng/L升高至( 3.56±0.71)ng/L。PD-L1/GAPDH和 PD-1/GAPDH的比值也从 1.03±0.04、0.96±0.04降至 0.72±0.02、0.27±0.04(P<0.05)。结论车叶草苷酸可通过抑制胰腺癌及其免疫逃逸机制并激活 cGASSTING信号通路，是治疗胰腺癌的潜在药物。 |
| 英文摘要: |
| Objective To investigate the effect of asperulosidic acid (ASPA) on immune escape of pancreatic cancer (PC) and its reg-ulatory mechanism.Methods This research was conducted from February 2023 to August 2023, Human pancreatic ductal epithelialcells (HPDE) and PC cells (SW1990 and Capan-1) were treated with different concentrations of ASPA. Mouse xenograft tumor modelwas established. Cell viability was detected by CCK-8 assay. Cell proliferation was detected by EdU method. Apoptosis and CD4+ and CD4+CD25+Foxp3+ Treg levels were detected by flow cytometry. Transwell assay was used to detect cell migration and invasion. The lev-els of related proteins were determined by western blot. The levels of TGF-β1 and IL-10 in peripheral blood of mice were determined by enzyme-linked immunosorbent assay. Results The cell viability of SW1990 and Capan-1 was (99.00 ± 0.92)% and (99.00 ± 0.87)%, respectively, before ASPA treatment, and the viability of SW1990 and Capan-1 cells was reduced to (38 ± 1.63)% and (42.67 ±1.58)%, respectively, after treatment with 200 mg/L of psyllium glycoside, which was statistically significant (P<0.01). Chelidonate in-hibited the proliferation, migration and invasion of pancreatic cancer cells and significantly promoted apoptosis (P<0.05), the number ofproliferating cells (42.67 ± 4.56) and (46 ± 4.55), and the percentage of apoptotic cells (5.3±1.10)% and (5.22±0.76)% in SW1990 andCapan-1 before ASPA treatment, and the percentage of apoptotic cells (5.3±1.10)% and (5.22±0.76)% in ASPV treatment after ASPV treatment, the number of value-added cells significantly decreased to (22 ± 2.45) and (25.67 ± 2.59), and the percentage of apoptoticcells significantly increased to (16.41 ± 0.78)% and (15.13 ± 1.04)%. Compared with the tumor volume (845 ± 95.96) mm3 and tumor mass (0.86 ± 0.08) g in control mice, carnosic acid significantly inhibited the growth of pancreatic cancer tumors in vivo (P < 0.05), with the tumor volume decreasing to (520.67 ± 80.87) mm3 and the tumor mass decreasing to (0.53 ± 0.07) g. Carvosic acid activated the cGAS-STING pathway in pancreatic cancer (P<0.05). Psyllium glycoside treatment reduced the peripheral blood levels of TGF-β1, IL-10 and CD4+ in normal pancreatic cancer mice from (37.22 ± 3.26) ng/L, (153.65 ± 6.09) ng/L and (43.27 ± 5.62) ng/L to (25.77 ±2.31) ng/L, (123.36 ± 2.72) ng/L and (32.47 ± 3.21) ng/L, respectively. (32.47 ± 3.21) ng/L, and CD4+CD25+Foxp3+ Treg increased from (2.40 ± 0.36) ng/L to (3.56 ± 0.71) ng/L. The ratios of PD-L1/GAPDH and PD-1/GAPDH also decreased from (1.03 ± 0.04), (0.96 ± 0.04) to (0.72 ± 0.02), (0.27 ± 0.04) (P<0.05).Conclusion Asperuloside acid is a potential drug for the treatment of pancreatic cancerby inhibiting the immune escape mechanism of pancreatic cancer and activating the cGAS-STING signaling pathway. |
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