中国临床药理学杂志

阿帕替尼调控HMGB1/RAGE通路对胃癌细胞增殖、凋亡和免疫逃逸影响的研究

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闫明霞 ¹ , 董升镇 ² , 林娜娜 ³ , 贺延新 ⁴ , 鲁杰 ⁵

中国临床药理学杂志 | 临床与基础桥接研究 2026,42(8): 1122-1129

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中国临床药理学杂志 |临床与基础桥接研究 2026 , 42 (8) : 1122 -1129

阿帕替尼调控HMGB1/RAGE通路对胃癌细胞增殖、凋亡和免疫逃逸影响的研究

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闫明霞¹, 董升镇², 林娜娜³, 贺延新⁴, 鲁杰⁵

作者信息

^1.康复大学青岛医院（青岛市市立医院）急诊科，山东青岛 266071

^2.康复大学青岛中心医院放射物理科，山东青岛 266042

^3.康复大学青岛中心医院放射科，山东青岛 266042

^4.康复大学青岛中心医院消化内科，山东青岛 266042

^5.康复大学青岛医院（青岛市市立医院）本部胃肠外科，山东青岛 266011

通讯作者:

鲁杰，副主任医师 MP: 17561788065 E-mail: mmun7@163.com

作者简介:

闫明霞（1989-）女，主治医师，从事胃肠外科、疝与腹壁外科的临床工作和研究

Research of the effects of apatinib on the proliferation, apoptosis, and immune escape of gastric cancer cells by adjusting the HMGB1/RAGE pathway

Ming-xia YAN¹, Sheng-zhen DONG², Na-na LIN³, Yan-xin HE⁴, Jie LU⁵

Affiliations

^1.Emergency Department, Qingdao Hospital of Rehabilitation University (Qingdao Municipal Hospital), Qingdao 266071, Shandong Province, China

^2.Radiation Physics Department, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao 266042, Shandong Province, China

^3.Radiology Department, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao 266042, Shandong Province, China

^4.Department of Gastroenterology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao 266042, Shandong Province, China

^5.Department of Gastrointestinal Surgery, Qingdao Hospital of Rehabilitation University (Qingdao Municipal Hospital), Qingdao 266011, Shandong Province, China

出版时间: 2026-04-28 doi: 10.13699/j.cnki.1001-6821.2026.08.012

文章导航

摘要

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目的

研究阿帕替尼（APa）调控高迁移率族蛋白B1（HMGB1）/晚期糖基化终末产物受体（RAGE）通路对胃癌细胞增殖、凋亡和免疫逃逸的影响。

方法

将SGC-7901细胞随机分为空白对照组、低剂量实验组（20 μmol·L^-1Apa干预48 h）、中剂量实验组（40 μmol·L^-1 Apa干预48 h）、高剂量实验组（60 μmol·L^-1 Apa干预48 h）、HMGB1组（60 μmol·L^-1 Apa与100 ng·mL^-1 HMGB1重组因子联合干预48 h），以APa和人HMGB1重组因子分组干预后利用细胞计数试剂盒-8（CCK-8）法、5-乙炔基-2′-脱氧尿苷（Edu）染色、免疫荧光染色Ki67检测各组SGC-7901细胞增殖；利用流式细胞实验、Hoechst 33342/PI双染、免疫荧光法检测各组SGC-7901细胞凋亡；利用蛋白质印迹实验检测各组SGC-7901细胞HMGB1/RAGE信号通路蛋白表达。构建活化外周血单个核细胞（PBMC）或NK细胞与SGC-7901细胞的共培养体系，同法分组及药物干预后利用CCK-8法检测T细胞与NK细胞对各组SGC-7901细胞杀伤率；利用流式细胞实验检测各组PBMC与SGC-7901细胞共培养体系中活化CD8⁺T细胞比例；免疫荧光染色检测各组PBMC与SGC-7901细胞共培养体系中SGC-7901细胞程序性死亡受体1（PD-1）、程序性死亡配体-1（PD-L1）表达；利用酶联免疫吸附测定（ELISA）法测定PBMC与SGC-7901细胞共培养体系中免疫细胞因子白细胞介素（IL）-6、γ干扰素（IFN-γ）、肿瘤坏死因子-α（TNF-α）、IL-2产生水平。

结果

空白组、低、中、高剂量实验组和HMGB1组Edu阳性率分别为（86.23±5.30）%、（65.81±4.65）%、（43.16±4.52）%、（20.19±3.79）%和（82.45±5.27）%，凋亡率分别为（4.37±1.19）%、（23.05±2.14）%、（41.87±2.69）%、（62.04±3.12）%和（5.91±1.28）%，HMGB1蛋白相对表达水平分别为1.15±0.07、0.79±0.05、0.43±0.04、0.10±0.02和1.13±0.06，RAGE蛋白相对表达水平分别为1.23±0.08、0.85±0.06、0.47±0.05、0.14±0.03和1.21±0.07，PD-1阳性表达率分别为（58.13±3.70）%、（45.37±2.84）%、（32.06±3.01）%、（21.47±2.31）%、和（54.87±3.53）%，T细胞杀伤率分别为（10.12±1.34）%、（23.45±1.62）%、（37.06±2.08）%、（51.29±2.73）%和（12.01±1.61）%，活化CD8⁺T细胞比例分别为（7.21±0.53）%、（12.42±0.81）%、（17.93±0.75）%、（23.07±0.64）%和（7.93±0.56）%，IL-6水平分别为（28.31±3.26）、（46.02±4.18）、（65.43±3.70）、（86.15±4.39）和（31.04±3.48）ng·L^-1，上述指标，低、中、高剂量实验组与空白对照组比较，HMGB1组与高剂量实验组比较降低，在统计学上差异均有统计学意义（均P<0.05）。

结论

APa可抑制胃癌细胞增殖及免疫逃逸，促进其凋亡，可能是通过阻止HMGB1/RAGE信号通路激活实现的。

关键词

阿帕替尼 / 高迁移率族蛋白B1/晚期糖基化终末产物受体 / 胃癌 / 增殖 / 凋亡 / 免疫逃逸

Abstract

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Objective

To discuss the effects of apatinib (APa) on proliferation, apoptosis, and immune escape of gastric cancer cells by adjusting the high mobility group box 1 (HMGB1)/receptor for advanced glycosylation end products (RAGE) pathway.

Methods

SGC-7901 cells were randomly separated into blank control group, low-dose experimental group (intervention with 20 μmol·L^-1 Apa for 48 hours), medium-dose experimental group (intervention with 40 μmol·L^-1 Apa for 48 hours), high-dose experimental group (intervention with 60 μmol·L^-1 Apa for 48 hours) and HMGB1 group (intervention with 60 μmol·L^-1 Apa combined with 100 ng·mL^-1 HMGB1 recombinant factor for 48 hours). After intervention with APa and human HMGB1 recombinant factor, cell counting kit-8 (CCK-8) method, 5-Ethynyl-2’- deoxyuridine (Edu) staining, and immunofluorescence staining Ki67 were used to measure the proliferation of SGC-7901 cells in each group. Flow cytometry, Hoechst 33342/PI double staining, and immunofluorescence were performed to measure apoptosis of SGC-7901 cells in each group. Western blot was performed to detect the expression of HMGB1/RAGE signaling pathway proteins of SGC-7901 cells in various groups. A co-culture system of activated peripheral blood mononuclear cells (PBMCs) or NK cells with SGC-7901 cells was constructed. After grouping and drug intervention, the CCK-8 method was performed to detect the killing rates of T cells and NK cells against SGC-7901 cells in each group. Flow cytometry was used to measure the proportion of activated CD8⁺T cells in the co culture system of PBMCs and SGC-7901 cells in each group. Immunofluorescence staining was performed to measure the expression of programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in the co culture system of PBMC and SGC-7901 cells in various groups. In addition, enzyme linked immunosorbent assay (ELISA) method was used to measure the levels of immune cytokines interleukin (IL)-6, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and IL-2 production in the co culture system of PBMC and SGC-7901 cells.

Results

The Edu positive rates in blank control group, the low-dose experimental group, medium-dose experimental group, high-dose experimental group and HMGB1 group were (86.23±5.30)%, (65.81±4.65)%, (43.16±4.52)%, (20.19±3.79)% and (82.45±5.27)%, respectively; the apoptosis rates were (4.37±1.19)%, (23.05±2.14)%, (41.87±2.69)%, (62.04±3.12)% and (5.91±1.28)%, respectively; the relative expression levels of HMGB1 protein were 1.15±0.07, 0.79±0.05, 0.43±0.04, 0.10±0.02 and 1.13±0.06, respectively; the RAGE protein expression levels were 1.23±0.08, 0.85±0.06, 0.47±0.05, 0.14±0.03 and 1.21±0.07, respectively; the PD-1 positive expression rates were (58.13±3.70)%, (45.37±2.84)%, (32.06±3.01)%, (21.47±2.31)% and (54.87±3.53)%, respectively; the T cell killing rates were (10.12±1.34)%, (23.45±1.62)%, (37.06±2.08)%, (51.29±2.73)% and (12.01±1.61)%, respectively; the proportions of activated CD8⁺T cells were (7.21±0.53)%, (12.42±0.81)%, (17.93±0.75)%, (23.07±0.64)% and (7.93±0.56)%, respectively; the IL-6 production levels were (28.31±3.26), (46.02±4.18), (65.43±3.70), (86.15±4.39) and (31.04±3.48) ng·L^-1, respectively. Compared the blank control group with the low-dose experimental group, medium-dose experimental group and high-dose experimental group, compared the HMGB1 group with the high-dose experimental group, the differences of above indexes were all statistically significant (all P<0.05).

Conclusion

APa can inhibit the proliferation and immune escape of gastric cancer cells, promote their apoptosis, possibly by blocking the activation of the HMGB1/RAGE signaling pathway.

Key words

apatinib / high mobility group box 1/receptor for advanced glycosylation end products / gastric cancer / proliferation / apoptosis / immune escape

引用本文

闫明霞, 董升镇, 林娜娜, 贺延新, 鲁杰. 阿帕替尼调控HMGB1/RAGE通路对胃癌细胞增殖、凋亡和免疫逃逸影响的研究. 中国临床药理学杂志, 2026 , 42 (8) : 1122 -1129 . DOI: 10.13699/j.cnki.1001-6821.2026.08.012

Ming-xia YAN, Sheng-zhen DONG, Na-na LIN, Yan-xin HE, Jie LU. Research of the effects of apatinib on the proliferation, apoptosis, and immune escape of gastric cancer cells by adjusting the HMGB1/RAGE pathway[J]. Chinese Journal of Clinical Pharmacology, 2026 , 42 (8) : 1122 -1129 . DOI: 10.13699/j.cnki.1001-6821.2026.08.012

基金

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青岛市医药卫生科研指导项目(2023-WJZD189)

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2026年第42卷第8期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2026.08.012

接收时间：2025-09-22
首发时间：2026-08-06
出版时间：2026-04-28

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收稿日期：2025-09-22

基金

青岛市医药卫生科研指导项目(2023-WJZD189)

作者信息

^1.康复大学青岛医院（青岛市市立医院）急诊科，山东青岛 266071

^2.康复大学青岛中心医院放射物理科，山东青岛 266042

^3.康复大学青岛中心医院放射科，山东青岛 266042

^4.康复大学青岛中心医院消化内科，山东青岛 266042

^5.康复大学青岛医院（青岛市市立医院）本部胃肠外科，山东青岛 266011

通讯作者:

鲁杰，副主任医师 MP: 17561788065 E-mail: mmun7@163.com

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鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
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