1.中山大学药学院,广东 广州510006
2.中国海洋大学海德学院,山东 青岛266003
3.中山大学孙逸仙纪念医院,广东 广州 510120
卢敏源,第一作者,研究方向:药理毒理学,E-mail: lumy26@mail2.sysu.edu.cn
马晓帆,通信作者,硕士生导师,教授,研究方向:肺癌发病机制及干预策略,E-mail: maxf8@mail.sysu.edu.cn
收稿:2025-09-19,
修回:2025-11-05,
录用:2025-11-06,
网络出版:2025-11-12,
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卢敏源, 王若楠, 张小雷, 等. 冬虫夏草提取物在克服肺癌免疫治疗耐药中的作用[J/OL]. 中山大学学报(医学科学版), 2025,1-6.
LU Minyuan, WANG Ruonan, ZHANG Xiaolei, et al. Effect of
目的
2
探讨冬虫夏草提取物对非小细胞肺癌(NSCLC)免疫治疗耐药的逆转作用。
方法
2
采用ELISA、流式细胞术、共培养实验检测冬虫夏草提取物对人源T淋巴细胞(JKT)细胞因子分泌、增殖和对肿瘤细胞杀伤活性的影响,进一步通过体内实验检测冬虫夏草提取物单独使用及联合程序性死亡配体-1(PD-L1)单抗对PD-L1耐药肺癌的疗效。
结果
2
冬虫夏草提取物可以增强JKT细胞的细胞因子γ-
干扰素(IFN-γ)、肿瘤坏死因子α(TNF-α)、白细胞介素-2(IL-2)分泌,促进其细胞增殖(
P
= 0.006),增强其对肿瘤的杀伤能力(
P
<
0.001)。在体内实验中,与对照组相比,冬虫夏草提取物单药治疗可抑制PD-L1耐药肿瘤的生长[肿瘤生长抑制率(TGI)=26.1%,
P
= 0.090],而与PD-L1单抗联用可显著逆转PD-L1耐药(TGI=50.6%,
P
<
0.001)。
结论
2
本研究为冬虫夏草激活抗肿瘤免疫提供了一定的数据支撑,为增强肺癌抗肿瘤免疫,逆转肺癌免疫耐药提供了一种新的治疗策略。
Objective
2
To investigate the reversal effect of
Cordyceps sinensis
extract on immunotherapy resistance of non-small cell lung cancer (NSCLC).
Methods
2
ELISA, flow cytometry, and co-culture assays were performed to evaluate the effects of
Cordyceps sinensis
extract on cytokine secretion, proliferation, and tumor cell killing activity of Jurkat (JKT) cells. Furthermore, the therapeutic effect of
Cordyceps sinensis
extract on programmed cell death ligand 1 (PD-L1) resistant lung cancer was evaluated through
in vivo
experiments both alone and in combination with anti-PD-L1 monoclonal antibody.
Results
2
Cordyceps sinensis
extract enhanced the secretion of cytokines interferon gamma(IFN-γ), tumor necrosis factor-alpha(TNF-α) and interleukin-2 (IL-2)in JKT cells, promoted cell proliferation (
P
= 0.006), and boosted their killing function against tumors (
P
<
0.001). Compared with the control group,
in vivo
study demonstrated that
Cordyceps sinensis
extract monotherapy effectively inhibited the growth of PD-L1-resistant tumors [tumor growth inhibition value (TGI) = 26.1%,
P
= 0.090], while its combination with anti-PD-L1 antibody significantly reversed PD-L1 resistance (TGI = 50.6%,
P
<
0.001).
Conclusion
2
This study provides certain data support for the activation of anti-tumor immunity by
Cordyceps sinensis
extract, and offers a new treatment strategy for enhancing anti-tumor immunity and reversing immune resistance in lung cancer.
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