GFPT1通过调节PD-L1通路对非小细胞肺癌细胞的影响

doi:10.11958/20260080

天津医药 ›› 2026, Vol. 54 ›› Issue (7): 687-692.doi: 10.11958/20260080

GFPT1通过调节PD-L1通路对非小细胞肺癌细胞的影响

张渤¹(), 徐伟²^,^△(), 张静¹, 马肖¹

¹ 沧州市人民医院医学检验中心（邮编061000）
² 沧州市人民医院医学检验中心肿瘤内科二区（邮编061000）

收稿日期:2026-01-06 修回日期:2026-02-05 出版日期:2026-07-15 发布日期:2026-07-13
通讯作者: ^△E-mail：814608242@qq.com
作者简介:张渤（1990），女，主治医师，主要从事生化免疫方面研究。E-mail：zhang1857bo@163.com
基金资助:
沧州市科技计划自筹经费项目(23244102014)

The effects of GFPT1 on non-small cell lung cancer cells by adjusting the PD-L1 pathway

ZHANG Bo¹(), XU Wei²^,^△(), ZHANG Jing¹, MA Xiao¹

¹ Medical Testing Center, Cangzhou People's Hospital, Cangzhou 061000, China
² Division II, Department of Oncology, Cangzhou People's Hospital, Cangzhou 061000, China

Received:2026-01-06 Revised:2026-02-05 Published:2026-07-15 Online:2026-07-13
Contact: ^△E-mail：814608242@qq.com

张渤, 徐伟, 张静, 马肖. GFPT1通过调节PD-L1通路对非小细胞肺癌细胞的影响[J]. 天津医药, 2026, 54(7): 687-692.

ZHANG Bo, XU Wei, ZHANG Jing, MA Xiao. The effects of GFPT1 on non-small cell lung cancer cells by adjusting the PD-L1 pathway[J]. Tianjin Medical Journal, 2026, 54(7): 687-692.

摘要/Abstract

摘要：

目的探究谷氨酰胺果糖-6-磷酸转氨酶1（GFPT1）通过调节程序性细胞死亡配体1（PD-L1）通路对非小细胞肺癌细胞增殖、凋亡及免疫逃逸的影响。方法采集进行手术治疗的80例非小细胞肺癌患者癌及癌旁组织样本，免疫组化检测GFPT1表达情况，培养人非小细胞肺癌细胞系A549并分为CK组、sh-NC组、sh-GFPT1组、sh-GFPT1+oe-NC组、sh-GFPT1+oe-PD-L1组。EdU染色检测细胞增殖；流式细胞术检测细胞凋亡；Western blot检测蛋白表达。从健康体检者外周血分离纯化人原代CD8?T细胞，与各组A549细胞共培养48 h，收集共培养上清液，通过Ficoll密度梯度离心纯化回收CD8?T细胞；台盼蓝染色检测CD8⁺T细胞存活率；酶联免疫吸附试验检测共培养液中转化生长因子-β（TGF-β）、白细胞介素-10（IL-10）、干扰素-γ（IFN-γ）、PD-L1水平。结果癌组织较癌旁组织GFPT1细胞阳性率升高，Ⅲ—Ⅳ期较Ⅰ—Ⅱ期患者癌组织中GFPT1细胞阳性率升高（P<0.01）。sh-GFPT1组较CK组、sh-NC组EdU阳性率、增殖细胞核抗原（PCNA）、Ki-67增殖抗原（Ki-67）、B细胞淋巴瘤蛋白2（Bcl-2）、PD-L1降低，细胞凋亡率、Bcl-2相关X蛋白（Bax）升高（P<0.05）；sh-GFPT1+oe-PD-L1组较sh-GFPT1组、sh-GFPT1+oe-NC组上述指标呈反向变化。与CD8⁺T细胞共培养后，sh-GFPT1组较CK组、sh-NC组CD8⁺T细胞存活率、IFN-γ升高，TGF-β、IL-10、PD-L1降低（P<0.05）；sh-GFPT1+oe-PD-L1组较sh-GFPT1组、sh-GFPT1+oe-NC组CD8⁺T细胞存活率、IFN-γ降低，TGF-β、IL-10、PD-L1升高（P<0.05）。结论 GFPT1在非小细胞肺癌组织中高表达，沉默GFPT1可抑制PD-L1，进而抑制非小细胞肺癌细胞增殖、免疫逃逸，促进其凋亡。

关键词: 癌, 非小细胞肺, 谷氨酰胺-果糖-6-磷酸转氨酶（异构）, B7-H1抗原, 细胞增殖, 细胞凋亡, 肿瘤逃逸

Abstract:

Objective To discuss the effects of glutamine fructose-6-phosphate transaminase 1 (GFPT1) on the proliferation, apoptosis and immune escape of non-small cell lung cancer cells by adjusting the programmed cell death ligand 1 (PD-L1) pathway. Methods Cancer and adjacent tissue samples of 80 patients with non-small cell lung cancer who underwent surgical treatment were collected, and the expression of GFPT1 was detected by immunohistochemistry. Human non-small cell lung cancer cell line A549 was cultured and divided into the CK group, the sh-NC group, the sh-GFPT1 group, the sh-GFPT1+oe-NC group and the sh-GFPT1+oe-PD-L1 group. EdU staining was performed to detect cell proliferation. Cell apoptosis was measured by flow cytometry. Protein expression levels were measured by Western blot assay. Primary human CD8?T cells were isolated and purified from peripheral blood of healthy volunteers and co-cultured with A549 cells from each group for 48 h. The co-culture supernatant was collected, and CD8?T cells were purified and recovered via Ficoll density-gradient centrifugation. Trypan blue staining was used to detect the survival rate of the recovered CD8? T cells from co-culture. Enzyme-linked immunosorbent assay was performed to measure the levels of transforming growth factor-β (TGF-β), interleukin-10 (IL-10), interferon-γ (IFN-γ) and PD-L1 in the co-culture medium. Results The positive rate of GFPT1 was higher in cancer tissue than that in adjacent non-cancerous tissue, and the positive rate of GFPT1 was also higher in cancer tissue from stage Ⅲ—Ⅳ patients compared to those of stage Ⅰ—Ⅱ patients (P<0.01). The positive rate of EdU, the expressions of proliferating cell nuclear antigen (PCNA), Ki-67 proliferation antigen (Ki-67), B-cell lymphoma 2 (Bcl-2) and PD-L1 were lower in the sh-GFPT1 group than those in the CK group and the sh-NC group, while the apoptosis rate and the expression of Bcl-2-associated X protein (Bax) were higher (P < 0.05). The above indicators showed the opposite changes in the sh-GFPT1+oe-PD-L1 group compared with the sh-GFPT1 group and the sh-GFPT1+oe-NC group. After co-culture with CD8⁺T cells, the survival rate of CD8?T cells and IFN-γ level were higher in the sh-GFPT1 group than those in the CK group and the sh-NC group, while the levels of TGF-β, IL-10 and PD-L1 were lower (P<0.05). The survival rate of CD8?T cells and IFN-γ level were lower in the sh-GFPT1+oe-PD-L1 group than those in the sh-GFPT1 group and the sh-GFPT1+oe-NC group, while the levels of TGF-β, IL-10 and PD-L1 were higher (P < 0.05). Conclusion GFPT1 is highly expressed in non-small cell lung cancer tissue. Silencing the expression of GFPT1 can inhibit PD-L1 expression, thereby inhibiting the proliferation and immune escape of non-small cell lung cancer cells and promoting their apoptosis.

Key words: carcinoma, non-small-cell lung, glutamine-fructose-6-phosphate transaminase (isomerizing), B7-H1 antigen, cell proliferation, apoptosis, tumor escape

中图分类号:

R734.2

图/表 9

参考文献 26

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组别	EdU阳性率	细胞凋亡率	CD8⁺T细胞存活率
CK组	26.41±2.67	6.16±1.76	33.49±5.78
sh-NC组	26.39±2.65	6.14±1.74	33.51±5.82
sh-GFPT1组	9.14±2.47^ab	19.67±1.97^ab	60.35±6.05^ab
sh-GFPT1+oe-NC组	9.15±2.50	19.68±1.98	60.36±6.07
sh-GFPT1+oe-PD-L1组	15.78±2.59^cd	12.79±1.85^cd	46.17±5.96^cd
F	67.956^＊＊	79.084^＊＊	30.709^＊＊

组别	EdU阳性率	细胞凋亡率	CD8⁺T细胞存活率
CK组	26.41±2.67	6.16±1.76	33.49±5.78
sh-NC组	26.39±2.65	6.14±1.74	33.51±5.82
sh-GFPT1组	9.14±2.47^ab	19.67±1.97^ab	60.35±6.05^ab
sh-GFPT1+oe-NC组	9.15±2.50	19.68±1.98	60.36±6.07
sh-GFPT1+oe-PD-L1组	15.78±2.59^cd	12.79±1.85^cd	46.17±5.96^cd
F	67.956^＊＊	79.084^＊＊	30.709^＊＊

组别		PCNA		Ki-67
CK组		0.72±0.08		0.76±0.08
sh-NC组		0.71±0.07		0.78±0.09
sh-GFPT1组		0.35±0.04^ab		0.52±0.05^ab
sh-GFPT1+oe-NC组		0.37±0.05		0.53±0.06
sh-GFPT1+oe-PD-L1组		0.59±0.06^cd		0.69±0.07^cd
F		50.716^＊＊		18.153^＊＊
组别	Bcl-2		Bax		PD-L1
CK组	0.69±0.07		0.35±0.05		0.95±0.10
sh-NC组	0.70±0.08		0.33±0.04		0.97±0.11
sh-GFPT1组	0.43±0.05^ab		0.66±0.08^ab		0.71±0.07^ab
sh-GFPT1+oe-NC组	0.41±0.04		0.64±0.07		0.72±0.08
sh-GFPT1+oe-PD-L1组	0.57±0.06^cd		0.50±0.06^cd		0.83±0.09^cd
F	30.000^＊＊		38.100^＊＊		10.901^＊＊

组别		PCNA		Ki-67
CK组		0.72±0.08		0.76±0.08
sh-NC组		0.71±0.07		0.78±0.09
sh-GFPT1组		0.35±0.04^ab		0.52±0.05^ab
sh-GFPT1+oe-NC组		0.37±0.05		0.53±0.06
sh-GFPT1+oe-PD-L1组		0.59±0.06^cd		0.69±0.07^cd
F		50.716^＊＊		18.153^＊＊
组别	Bcl-2		Bax		PD-L1
CK组	0.69±0.07		0.35±0.05		0.95±0.10
sh-NC组	0.70±0.08		0.33±0.04		0.97±0.11
sh-GFPT1组	0.43±0.05^ab		0.66±0.08^ab		0.71±0.07^ab
sh-GFPT1+oe-NC组	0.41±0.04		0.64±0.07		0.72±0.08
sh-GFPT1+oe-PD-L1组	0.57±0.06^cd		0.50±0.06^cd		0.83±0.09^cd
F	30.000^＊＊		38.100^＊＊		10.901^＊＊

组别		TGF-β	IL-10
CK组		412.69±42.31		119.55±12.02
sh-NC组		412.63±42.27	119.52±11.98
sh-GFPT1组		216.35±40.95^ab	72.14±11.29^ab
sh-GFPT1+oe-NC组		216.17±40.88	72.17±11.35
sh-GFPT1+oe-PD-L1组		367.28±41.08^cd	93.04±11.61^cd
F		35.534^＊＊	24.863^＊＊
组别	IFN-γ			PD-L1
CK组	185.61±30.73			83.72±8.51
sh-NC组	185.64±30.76			83.69±8.47
sh-GFPT1组	316.43±31.71^ab			51.23±8.16^ab
sh-GFPT1+oe-NC组	316.50±31.75			51.19±8.13
sh-GFPT1+oe-PD-L1组	220.71±30.98^cd			72.65±8.30^cd
F	27.183^＊＊			23.374^＊＊

GFPT1通过调节PD-L1通路对非小细胞肺癌细胞的影响

The effects of GFPT1 on non-small cell lung cancer cells by adjusting the PD-L1 pathway

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