中华中医药学刊

从抑制肿瘤微环境中癌相关纤维细胞探讨固本清源方延缓前列腺癌新型内分泌治疗耐药作用机制

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陈浩然 ¹ , 刘浩 ¹ , 朱旭东 ¹ , 王家政 ¹ , 陈亚飞 ² , 王艺林 ²

中华中医药学刊 | 国家项目点击 2026,44(4): 124-129

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中华中医药学刊 |国家项目点击 2026 , 44 (4) : 124 -129

从抑制肿瘤微环境中癌相关纤维细胞探讨固本清源方延缓前列腺癌新型内分泌治疗耐药作用机制

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陈浩然¹, 刘浩¹, 朱旭东¹, 王家政¹, 陈亚飞², 王艺林²

作者信息

^1.中国中医科学院广安门医院，北京 100053

^2.北京中医药大学研究生院，北京 100029

通讯作者:

刘浩（1975-），男，河北保定人，主任医师，博士研究生导师，博士，研究方向：中西医结合治疗前列腺癌。E-mail: drliuhao@126.com。

作者简介:

陈浩然（1995-），男，广东广州人，博士在读，研究方向：中西医结合治疗前列腺癌临床与转化。

Exploring Mechanism of Delayed Resistance to Novel Endocrine Therapy for Prostate Cancer by Guben Qingyuan Prescription（固本清源方）From inhibition of CAF in Tumor Microenvironment

Haoran CHEN¹, Hao LIU¹, Xudong ZHU¹, Jiazheng WANG¹, Yafei CHEN², Yilin WANG²

Affiliations

^1.Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China

^2.Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China

出版时间: 2026-04-10 doi: 10.13193/j.issn.1673-7717.2026.04.027

文章导航

摘要

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目的

探讨固本清源方抑制恩扎卢胺耐药过程中癌相关成纤维细胞（cancer-associated fibroblast，CAF）的作用研究。

方法

建立前列腺癌恩扎卢胺耐药细胞荷瘤小鼠模型，观察固本清源方联合恩扎卢胺干预对荷瘤小鼠肿瘤生长的影响以及肿瘤组织中CAF的影响；采用免疫荧光检测固本清源方对CAF诱导转化的影响，CCK8法检测固本清源方对CAF增殖的影响，酶联免疫吸附试验检测固本清源方对CAF衍生因子的影响。

结果

固本清源方联合恩扎卢胺干预对恩扎卢胺耐药细胞荷瘤小鼠肿瘤的抑制率在29%～47%，其中中、高剂量固本清源方联合恩扎卢胺组与恩扎卢胺组比较差异具有显著统计学意义（P<0.01）。免疫荧光及免疫组化结果显示恩扎卢胺耐药细胞荷瘤小鼠肿瘤组织中CAF的标志物成纤维细胞激活蛋白（fibroblast activation protein-α，FAP）、α-平滑肌肌动蛋白（α-smooth muscle actin，α-SMA）表达显著高于接种前列腺癌C4-2B细胞组，中、高剂量固本清源方联合恩扎卢胺组能抑制FAP、α-SMA表达，与恩扎卢胺组比较差异具有统计学意义（P<0.05）。免疫荧光显示中、高剂量固本清源方含药血清能抑制体外CAF的FAP、α-SMA表达；采用固本清源方含药血清干预CAF 48、72 h后，中、高剂量固本清源方组的抑制率显著升高，与对照组比较差异具有统计学意义（P<0.05）；进一步研究显示固本清源方能抑制CAF上清液中转化生长因子-β1（transforming growth factor-β1，TGF-β1）、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、基质细胞衍生因子-1（stromal cell-derived factor-1，SDF-1）、无翅/集成基因（wingless/integrated-3a，Wnt3a）、基质金属蛋白酶2（matrix metalloproteinase 2，MMP-2）的含量。

结论

固本清源方对延缓前列腺癌新型内分泌治疗恩扎卢胺耐药具有一定作用，作用靶点与CAF有关。

关键词

前列腺癌 / 新型内分泌治疗 / 治疗耐药 / 癌相关成纤维细胞 / 中医药 / 固本清源方

Abstract

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Objective

To investigate the effect of Guben Qingyuan Prescription（固本清源方）on inhibiting cancer-associated fibroblast（CAF） in the development of resistance to enzalutamide.

Methods

A tumor-bearing mouse model of enzalutamide-resistant prostate cancer cells was established to observe the effects of Guben Qingyuan Prescription combined with enzalutamide on tumor growth and CAF in tumor tissues. The effects of Guben Qingyuan Prescription on CAF transformation were assessed using immunofluorescence. CAF proliferation was evaluated by the CCK8 assay, and the influence of Guben Qingyuan Prescription on CAF-derived factors was measured via enzyme-linked immunosorbent assay（ELISA）.

Results

The tumor inhibition rate of the Guben Qingyuan Prescription combined with enzalutamide ranged from 29% to 47%. In the medium - and high-dose groups, the combination treatment showed a statistically significant difference compared to the enzalutamide-only group（P<0.01）. Immunofluorescence and immunohistochemistry results demonstrated that the expressions of CAF markers fibroblast activation protein-α（FAP）and α-smooth muscle actin（α-SMA）in tumor tissues of enzalutamide-resistant mice were significantly higher than those in the group inoculated with prostate cancer C4-2B cells. The medium - and high-dose Guben Qingyuan Prescription combined with enzalutamide groups significantly inhibited the expressions of FAP and α-SMA compared to the enzalutamide-only group（P<0.05）. Additionally, immunofluorescence showed that serum containing medium - and high-dose Guben Qingyuan Prescription groups could inhibit the expressions of FAP and α-SMA in vitro. After 48 and 72 hours of treatment, the inhibition rates of the medium - and high-dose Guben Qingyuan Prescription groups significantly increased, with a statistically significant difference compared to the control group（P<0.05）. Further studies revealed that Guben Qingyuan Prescription reduced the concentrations of transforming growth factor-β1（TGF-β1）, tumor necrosis factor-α（TNF-α）, stromal cell-derived factor-1（SDF-1）, Wingless/Integrated-3a（Wnt3a）and matrix metalloproteinase 2（MMP2）in CAF supernatants.

Conclusion

Guben Qingyuan Prescription has a significant effect in delaying resistance to enzalutamide, a novel endocrine therapy for prostate cancer, and its mechanism of action may be related to the inhibition of CAF.

Key words

prostate cancer / novel endocrine therapy / drug resistance / CAF / Chinese medicine / Guben Qingyuan Prescription（固本清源方）

引用本文

陈浩然, 刘浩, 朱旭东, 王家政, 陈亚飞, 王艺林. 从抑制肿瘤微环境中癌相关纤维细胞探讨固本清源方延缓前列腺癌新型内分泌治疗耐药作用机制. 中华中医药学刊, 2026 , 44 (4) : 124 -129 . DOI: 10.13193/j.issn.1673-7717.2026.04.027

Haoran CHEN, Hao LIU, Xudong ZHU, Jiazheng WANG, Yafei CHEN, Yilin WANG. Exploring Mechanism of Delayed Resistance to Novel Endocrine Therapy for Prostate Cancer by Guben Qingyuan Prescription（固本清源方）From inhibition of CAF in Tumor Microenvironment[J]. Chinese Archives of Traditional Chinese Medicine, 2026 , 44 (4) : 124 -129 . DOI: 10.13193/j.issn.1673-7717.2026.04.027

基金

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国家自然科学基金面上项目(81873171)
国家中医药管理局全国中医药创新骨干人才项目(国中医药人教函〔2019〕128号)

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文献

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参考文献引证文献

排序方式：

[1]

SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA A Cancer J Clinicians, 2021, 71（3）: 209-249.

[2]

ZHU Y, MO M, WEI Y, et al. Epidemiology and genomics of prostate cancer in Asian men[J]. Nat Rev Urol, 2021, 18（5）: 282-301.

[3]

卞晓洁，叶定伟.前列腺癌雄激素剥夺治疗的新思路——睾酮最大控制临床研究新进展[J].中国癌症杂志，2021，31（12）：1209-1214.

[4]

SCHAEFFER E, SRINIVAS S, ADRA N, et al. NCCN Guidelines？Insights: Prostate Cancer, Version 1.2023.[J]. Journal of the National Comprehensive Cancer Network: JNCCN, 2022, 20（12）: 1288-1298.

[5]

中国临床肿瘤学会指南工作委员会.中国临床肿瘤学会（CSCO）前列腺癌诊疗指南2022 [M].北京：人民卫生出版社，2022：21-22.

[6]

JACOB A, RAJ R, ALLISON D B, et al. Androgen receptor signaling in prostate cancer and therapeutic strategies[J]. Cancers, 2021, 13（21）: 5417.

[7]

LI Q, XU J, HE Z, et al. The effects of matrine in combination with docetaxel on castration-resistant（androgen-independent）prostate cancer[J]. Cancer Manag Res, 2019, 11: 10125-10133.

[8]

刘浩，张培宇，张葛.复方苦参注射液对局部晚期前列腺癌内分泌治疗耐药改善作用的临床研究[J].中国中医药科技，2016，23（4）：385-387.

[9]

HU H, ZHOU H, XU D F. A review of the effects and molecular mechanisms of dimethylcurcumin（ASC-J9）on androgen receptor-related diseases[J]. Chem Biol Drug Des, 2021, 97（4）: 821-835.

[10]

刘浩，林洪生.林洪生主任固本清源治疗肿瘤学术思想[J].世界中医药，2016，11（01）：102-103.

[11]

陈浩然，方素萍，张迪，等.从AR/AR-V7信号通路探讨固本清源方联合雄激素剥夺治疗控制去势抵抗性前列腺癌的作用机制[J].中国实验方剂学杂志，2021，27（15）：16-21.

[12]

陈浩然，方素萍，张迪，等.从肿瘤干细胞Wnt通路探讨固本清源方药联合雄激素剥夺治疗控制去势抵抗性前列腺癌[J].中华中医药学刊，2023，41（3）：111-115.

[13]

TUXHORN J A, AYALA G E, SMITH MJ, et al. Reactive stroma in human prostate cancer: induction of myofibroblast phenotype and extracellular matrix remodeling1 [J]. Clinical Cancer Research, 2002, 8: 2912-2923.

[14]

陈赐慧，花宝金.关于中药血清药理学实验的几个问题和探讨[J].中华中医药学刊，2013，31（1）：46-48.

[15]

MEDINA C A, RITTER C D. Innovative alternatives for metastatic CRPC after enzalutamide[J]. Lancet Oncol, 2023, 24（1）: e9.

[16]

VAN SOEST R J, DE MORRÉE E S, KWELDAMC F, et al. Targeting the androgen receptor confers in vivo cross-resistance between enzalutamide and docetaxel, but not cabazitaxel, in castration-resistant prostate cancer[J]. Eur Urol, 2015, 67（6）: 981-985.

[17]

MAUGHAN B L, ANTONARAKIS E S. Olaparib and rucaparib for the treatment of DNA repair-deficient metastatic castration-resistant prostate cancer[J]. Expert Opin Pharmacother, 2021, 22（12）: 1625-1632.

[18]

刘浩，林洪生.中医肿瘤平衡治疗[J].世界中西医结合杂志，2015，10（7）：1006-1008.

[19]

NEUWIRT H, BOUCHAL J, KHARAISHVILI G, et al. Cancer-associated fibroblasts promote prostate tumor growth and progression through upregulation of cholesterol and steroid biosynthesis[J]. Cell Commun Signal, 2020, 18（1）: 11.

[20]

CULIG Z, PUHR M. Interleukin-6 and prostate cancer: Current developments and unsolved questions[J]. Mol Cell Endocrinol, 2018, 462: 25-30.

[21]

FENG B, WU J Z, SHEN B, et al. Cancer-associated fibroblasts and resistance to anticancer therapies: status, mechanisms, and countermeasures[J]. Cancer Cell Int, 2022, 22（1）: 166.

[22]

HENKE E, NANDIGAMA R, ERGÜN S. Extracellular matrix in the tumor microenvironment and its impact on cancer therapy[J]. Front Mol Biosci, 2020, 6: 160.

[23]

周仲瑛.“伏毒”新识[J].世界中医药，2007，2（2）：73-75.

[24]

叶古晃，周仲瑛.周仲瑛教授的“伏毒”学说[J].中国中医药现代远程教育，2005，3（12）：36.

[25]

GU C, LU H G, QIAN Z H. Matrine reduces the secretion of exosomal circSLC7A6 from cancer-associated fibroblast to inhibit tumorigenesis of colorectal cancer by regulating CXCR5[J]. Biochem Biophys Res Commun, 2020, 527（3）: 638-645.

[26]

BA P F, XU MC, YU M, et al. Curcumin suppresses the proliferation and tumorigenicity of Cal27 by modulating cancer-associated fibroblasts of TSCC[J]. Oral Dis, 2020, 26（7）: 1375-1383.

[27]

JALILIAN E, ABOLHASANI-ZADEH F, AFGAR A, et al. Neutralizing tumor-related inflammation and reprogramming of cancer-associated fibroblasts by Curcumin in breast cancer therapy[J]. Sci Rep, 2023, 13: 20770.

[28]

ZENG Y Q, DU Q D, ZHANG Z W, et al. Curcumin promotes cancer-associated fibroblasts apoptosis via ROS-mediated endoplasmic reticulum stress [J]. Arch Biochem Biophys, 2020, 694: 108613.

[29]

HAN S, HU M, QI G, et al. Polysaccharides from polygonatum inhibit the proliferation of prostate cancer-associated fibroblasts[J]. Asian Pac J Cancer Prev, 2016, 17（8）: 3829-3833.

2026年第44卷第4期

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文章信息

doi: 10.13193/j.issn.1673-7717.2026.04.027

首发时间：2026-10-14
出版时间：2026-04-10

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基金

国家自然科学基金面上项目(81873171)

国家中医药管理局全国中医药创新骨干人才项目(国中医药人教函〔2019〕128号)

作者信息

^1.中国中医科学院广安门医院，北京 100053

^2.北京中医药大学研究生院，北京 100029

通讯作者:

刘浩（1975-），男，河北保定人，主任医师，博士研究生导师，博士，研究方向：中西医结合治疗前列腺癌。E-mail: drliuhao@126.com。

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https://castjournals.cast.org.cn/joweb/zhzyyxk/CN/10.13193/j.issn.1673-7717.2026.04.027

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
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
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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