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安徽医科大学附属滁州医院/滁州市第一人民医院口腔科,安徽 滁州 239000
主治医师。研究方向:口外、口内修复。E-mail:18326905112@163.com
收稿日期:2025-05-27,
修回日期:2025-07-28,
录用日期:2025-07-28,
纸质出版日期:2025-09-15
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李锦宇,徐晓雨,王钰卓.枸杞多糖抑制口腔癌细胞增殖、迁移及免疫逃逸的机制研究[J].中国药房,2025,36(17):2134-2140.
LI Jinyu,XU Xiaoyu,WANG Yuzhuo.Study on the mechanism of Lycium barbarum polysaccharides inhibiting the proliferation, migration and immune escape of oral cancer cells[J].ZHONGGUO YAOFANG,2025,36(17):2134-2140.
李锦宇,徐晓雨,王钰卓.枸杞多糖抑制口腔癌细胞增殖、迁移及免疫逃逸的机制研究[J].中国药房,2025,36(17):2134-2140. DOI: 10.6039/j.issn.1001-0408.2025.17.09.
LI Jinyu,XU Xiaoyu,WANG Yuzhuo.Study on the mechanism of Lycium barbarum polysaccharides inhibiting the proliferation, migration and immune escape of oral cancer cells[J].ZHONGGUO YAOFANG,2025,36(17):2134-2140. DOI: 10.6039/j.issn.1001-0408.2025.17.09.
目的
2
探索枸杞多糖调节T细胞免疫球蛋白黏蛋白3(TIM3)/半乳糖凝集素9(Gal-9)信号通路对口腔癌细胞增殖、迁移和免疫逃逸的影响。
方法
2
将人口腔癌KB、CAL27细胞分为对照组、低浓度枸杞多糖组(200 μg/mL)、高浓度枸杞多糖组(400 μg/mL)、pcDNA-NC组(转染pcDNA-NC质粒)、pcDNA-TIM3组(转染pcDNA-TIM3质粒)、高浓度枸杞多糖+pcDNA-NC组(400 μg/mL枸杞多糖+转染pcDNA-NC质粒)、高浓度枸杞多糖+pcDNA-TIM3组(400 μg/mL枸杞多糖+转染pcDNA-TIM3质粒)。测定细胞的增殖、迁移、侵袭能力,T细胞杀伤率,细胞上清液中干扰素γ(IFN-γ)、白细胞介素2(IL-2)水平,以及细胞中TIM3、Gal-9 mRNA表达,以及细胞中吲哚胺2,3-双加氧酶1(IDO1)、程序性死亡受体配体1(PD-L1)、TIM3、Gal-9蛋白表达。
结果
2
与对照组比较,低、高浓度枸杞多糖组2种细胞的克隆形成率、划痕愈合率、侵袭细胞数以及IDO1、PD-L1蛋白和TIM3、Gal-9 mRNA及其蛋白表达水平均显著降低/减少(
P
<0.05),增殖抑制率、T细胞杀伤率和IFN-γ、IL-2水平均显著升高(
P
<0.05);与对照组、pcDNA-NC组比较,pcDNA-TIM3组2种细胞的克隆形成率、划痕愈合率、侵袭细胞数以及IDO1、PD-L1蛋白和TIM3、Gal-9 mRNA及其蛋白表达水平均显著升高/增加(
P
<0.05),增殖抑制率、T细胞杀伤率和IFN-γ、IL-2水平均显著降低(
P
<0.05);与高浓度枸杞多糖组、高浓度枸杞多糖+pcDNA-NC组比较,高浓度枸杞多糖+pcDNA-TIM3组2种细胞的克隆形成率、划痕愈合率、侵袭细胞数以及IDO1、PD-L1蛋白和TIM3、Gal-9 mRNA及其蛋白表达水平均显著升高/增加(
P
<0.05),增殖抑制率、T细胞杀伤率和IFN-γ、IL-2水平均显著降低(
P
<0.05)。
结论
2
枸杞多糖可能通过抑制TIM3/Gal-9信号通路来抑制口腔癌细胞增殖、迁移和免疫逃逸。
OBJECTIVE
2
To explore the effects of
Lycium barbarum
polysaccharides on the proliferation, migration, and immune escape of oral cancer cells by regulating the T cell immunoglobulin and mucin domain-containing protein 3 (TIM3)/galectin-9 (Gal-9) signaling pathway.
METHODS
2
Human oral cancer cells KB and CAL27 were assigned to control group,
L. barbarum
polysaccharides low-concentration group (200 μg/mL),
L. barbarum
polysaccharides high-concentration gr
oup (400 μg/mL), pcDNA-NC group (transfection of pcDNA-NC plasmid), pcDNA-TIM3 group (transfection of pcDNA-TIM3 plasmid), high concentration of
L. barbarum
polysaccharides+pcDNA-NC group (400 μg/mL
L. barbarum
polysaccharides + transfection of pcDNA-NC plasmid), and high concentration of
L. barbarum
polysaccharides+pcDNA-TIM3 group (400 μg/mL
L. barbarum
polysaccharides + transfection of pcDNA-TIM3 plasmid). The proliferation, migration and invasion abilities of the cells, T cell killing rate as well as the levels of interferon-γ (IFN-γ) and interleukin-2 (IL-2) in the cell supernatant were measured. mRNA expressions of TIM3 and Gal-9 and protein expressions of indoleamine 2,3-dioxygenase 1 (IDO1), programmed death-ligand 1 (PD-L1), TIM3 and Gal-9 in the cells were also determined.
RESULTS
2
Compared with control group, the clone formation rate, scratch healing rate, the number of invasive cells, protein expressions of IDO1 and PD-L1, mRNA and protein expressions of TIM3 and Gal-9 in both cell types of
L. barbarum
polysaccharide low- and high-concentration groups were decreased significantly (
P
<0.05), while the proliferation inhibition rate, T cell killing rate, and the levels of IFN-γ and IL-2 were significantly increased (
P
<0.05). Compared with control group and pcDNA-NC group, the clone formation rate, scratch healing rate, the number of invasive cells, and protein expressions of IDO1 and PD-L1, mRNA and protein expressions of TIM3 and Gal-9 in both cell types of the pcDNA-TIM3 group were all significantly increased (
P
<0.05), while the proliferation inhibition rate, T cell killing rate, IFN-γ and IL-2 levels were significantly decreased (
P
<0.05). Compared with
L. barbarum
polysaccharides high-concentration group and high concentration of
L. barbarum
polysaccharides+pcDNA-NC group, the clone fo
rmation rate, scratch healing rate, the number of invasive cells, and protein expressions of IDO1 and PD-L1, mRNA and protein expressions of TIM3 and Gal-9 in both cell types of high concentration of
L. barbarum
polysaccharides+pcDNA-TIM3 group were significantly increased (
P
<0.05), while the proliferation inhibition rate, T cell killing rate, and the levels of IFN-γ and IL-2 were significantly decreased (
P
<0.05).
CONCLUSIONS
2
L. barbarum
polysaccharides may inhibit the proliferation, migration, and immune escape of oral cancer cells by suppressing TIM3/Gal-9 signaling pathway.
RODRÍGUEZ-MOLINERO J , MIGUELÁÑEZ-MEDRÁN B D C , PUENTE-GUTIÉRREZ C , et al . Association between oral cancer and diet:an update [J ] . Nutrients , 2021 , 13 ( 4 ): 1299 .
WANG R , WANG Y . Fourier transform infrared spec- troscopy in oral cancer diagnosis [J ] . Int J Mol Sci , 2021 , 22 ( 3 ): 1206 .
ABATI S , BRAMATI C , BONDI S , et al . Oral cancer and precancer:a narrative review on the relevance of early diagnosis [J ] . Int J Environ Res Public Health , 2020 , 17 ( 24 ): 9160 .
MOTLOKWA P K , TSIMA B M , MARTEI Y M , et al . Disparities in oral cancer stage at presentation in a high HIV prevalence setting in sub-Saharan Africa [J ] . JCO Glob Oncol , 2022 , 8 : e2100439 .
MA L J , AI F F , XIAO H Y , et al . Lycium barbarum polysaccharide reverses drug resistance in oxaliplatin-resistant colon cancer cells by inhibiting PI3K/AKT-dependent phosphomannose isomerase [J ] . Front Pharmacol , 2024 , 15 : 1367747 .
姜鸣 , 李卓能 . 枸杞多糖通过p53信号通路调节人舌鳞状癌CAL-27细胞增殖和凋亡 [J ] . 临床口腔医学杂志 , 2022 , 38 ( 3 ): 140 - 143 .
KANDEL S , ADHIKARY P , LI G F , et al . The TIM3/Gal9 signaling pathway:an emerging target for cancer immunotherapy [J ] . Cancer Lett , 2021 , 510 : 67 - 78 .
DONG J F , CHENG L J , ZHAO M C , et al . Tim-3-expressing macrophages are functionally suppressed and expanded in oral squamous cell carcinoma due to virus-induced Gal-9 expression [J ] . Tumour Biol , 2017 , 39 ( 5 ): 1010428317701651 .
杨学鹏 , 王兰 , 柴居堂 , 等 . 积雪草苷调节TIM3/Gal9轴对肺癌细胞上皮-间充质转化和免疫逃逸的影响 [J ] . 中国细胞生物学学报 , 2024 , 46 ( 11 ): 1945 - 1953 .
辛国军 , 张亚文 , 雷鹏 , 等 . 枸杞多糖通过下调PD-L1表达抑制胆囊癌细胞增殖、侵袭及免疫逃逸的实验研究 [J ] . 临床肿瘤学杂志 , 2024 , 29 ( 6 ): 521 - 525 .
LIAO X Y , LIU C Y , HE J F , et al . Combination of checkpoint inhibitors with radiotherapy in esophageal squamous cell carcinoma treatment:a novel strategy [J ] . Oncol Lett , 2019 , 18 ( 5 ): 5011 - 5021 .
QIANG X , XIA T , GENG B B , et al . Bioactive components of Lycium barbarum and deep-processing fermentation products [J ] . Molecules , 2023 , 28 ( 24 ): 8044 .
SUN L N , ZUO C L , LIU X X , et al . Combined photothermal therapy and Lycium barbarum polysaccharide for topical administration to improve the efficacy of doxorubicin in the treatment of breast cancer [J ] . Pharmaceutics , 2022 , 14 ( 12 ): 2677 .
吴堰霖 , 宿颖 , 尹盼盼 , 等 . 干扰素γ诱导人口腔鳞癌细胞建立体外PD-L1高表达细胞模型及其对细胞生物学行为的影响 [J ] . 北京口腔医学 , 2022 , 30 ( 5 ): 305 - 309 .
FENG L , YIN K , ZHANG S , et al . Anti-PD-1 therapy is beneficial for the survival of patients with oral squamous cell carcinoma [J ] . Cancer Manag Res , 2022 , 14 : 2723 - 2731 .
HASEGAWA M , AMANO Y , KIHARA A , et al . Guany- late binding protein 5 is an immune-related biomarker of oral squamous cell carcinoma:a retrospective prognostic study with bioinformatic analysis [J ] . Cancer Med , 2024 , 13 ( 13 ): e7431 .
SAUER N , JANICKA N , SZLASA W , et al . TIM-3 as a promising target for cancer immunotherapy in a wide range of tumors [J ] . Cancer Immunol Immunother , 2023 , 72 ( 11 ): 3405 - 3425 .
ZHANG M P , LIU C , LI Y , et al . Galectin-9 in cancer therapy:from immune checkpoint ligand to promising therapeutic target [J ] . Front Cell Dev Biol , 2024 , 11 : 1332205 .
MITTELBERGER J , SEEFRIED M , LÖB S , et al . The expression of TIM-3 and Gal-9 on macrophages and Hofbauer cells in the placenta of preeclampsia patients [J ] . J Reprod Immunol , 2024 , 164 : 104296 .
NI X R , WU W C , SUN X Q , et al . Interrogating glioma-M2 macrophage interactions identifies Gal-9/Tim-3 as a viable target against PTEN-null glioblastoma [J ] . Sci Adv , 2022 , 8 ( 27 ): eabl5165 .
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