α-细辛酮通过转化生长因子- β 1/生长因子独立1轴减弱肿瘤相关巨噬细胞诱导的胰腺癌吉西他滨耐药

IF 2.2 4区 医学 Q3 ONCOLOGY
Anti-Cancer Drugs Pub Date : 2025-09-01 Epub Date: 2025-06-13 DOI:10.1097/CAD.0000000000001740
Jiaqi Yu, Yuzhe Xue, Zhaofeng Gao, Lingyu Hu, Xiaorong Liu, Xuesong He, Xiaoguang Wang
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引用次数: 0

摘要

胰腺癌具有侵袭性和预后差的特点。吉西他滨耐药的发展,特别是肿瘤微环境中肿瘤相关巨噬细胞(TAM)诱导的耐药,极大地限制了其治疗效果。本研究探讨植物源性生物活性化合物α-细辛酮在逆转tam诱导的胰腺癌吉西他滨耐药中的作用及其机制,为胰腺癌提供潜在的治疗选择。采用流式细胞术观察胰腺癌细胞的细胞周期和凋亡情况。采用ELISA法检测转化生长因子-β1 (TGF-β1)分泌,采用细胞计数试剂盒-8检测吉西他滨处理后PANC-1细胞的存活情况。采用Western blotting和实时荧光定量PCR分析生长因子独立1 (Gfi-1)表达及其与吉西他滨耐药的关系。α-细辛酮有效逆转胰腺癌细胞对吉西他滨的耐药。α-细辛酮可降低TAM条件下TGF-β1水平,进而导致Gfi-1表达上调。发现Gfi-1负向调控结缔组织生长因子(CTGF)、高迁移率组盒1 (HMGB1)等耐药因子的表达,从而逆转胰腺癌细胞对吉西他滨的耐药。上述结果表明,α-细辛酮可增强Gfi-1的表达,下调CTGF和HMGB1的表达,通过减少tam中TGF-β1的分泌,恢复吉西他滨敏感性。α-细辛酮可通过降低tam分泌TGF-β1,上调Gfi-1,下调CTGF、HMGB1等耐药因子,有效逆转胰腺癌对吉西他滨的耐药。这种吉西他滨敏感性的恢复可能会提高吉西他滨在胰腺癌治疗中的疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

α-Asarone attenuates tumor-associated macrophages-induced gemcitabine resistance in pancreatic carcinoma via the transforming growth factor-beta 1/growth factor independent 1 axis.

α-Asarone attenuates tumor-associated macrophages-induced gemcitabine resistance in pancreatic carcinoma via the transforming growth factor-beta 1/growth factor independent 1 axis.

α-Asarone attenuates tumor-associated macrophages-induced gemcitabine resistance in pancreatic carcinoma via the transforming growth factor-beta 1/growth factor independent 1 axis.

α-Asarone attenuates tumor-associated macrophages-induced gemcitabine resistance in pancreatic carcinoma via the transforming growth factor-beta 1/growth factor independent 1 axis.

α-Asarone attenuates tumor-associated macrophages-induced gemcitabine resistance in pancreatic carcinoma via the transforming growth factor-beta 1/growth factor independent 1 axis.

α-Asarone attenuates tumor-associated macrophages-induced gemcitabine resistance in pancreatic carcinoma via the transforming growth factor-beta 1/growth factor independent 1 axis.

α-Asarone attenuates tumor-associated macrophages-induced gemcitabine resistance in pancreatic carcinoma via the transforming growth factor-beta 1/growth factor independent 1 axis.

Pancreatic cancer is characterized by aggressiveness and poor prognosis. The development of gemcitabine resistance, especially tumor-associated macrophage (TAM) -induced resistance in the tumor microenvironment, has greatly limited its therapeutic effectiveness. This study investigates the effects and underlying mechanisms of the plant-derived bioactive compound α-asarone in reversing gemcitabine resistance induced by TAMs in pancreatic cancer, offering potential therapeutic alternatives. Flow cytometry was used to assess the cell cycle and apoptosis in pancreatic cancer cells. Transforming growth factor-beta 1 (TGF-β1) secretion was measured by ELISA, and Cell Counting Kit-8 assays to evaluate the survival of PANC-1 cells treated with gemcitabine. Western blotting and quantitative real-time PCR were used to analyze growth factor independent 1 (Gfi-1) expression and its association with gemcitabine resistance. α-Asarone effectively reversed gemcitabine resistance in pancreatic cancer cells. Treatment with α-asarone reduced TGF-β1 levels in TAM condition medium, which in turn led to the upregulation of Gfi-1 expression. Gfi-1 was found to negatively regulate the expression of drug resistance factors, including connective tissue growth factor (CTGF) and high mobility group box 1 (HMGB1), thereby reversing gemcitabine resistance in pancreatic cancer cells. Those results indicate that α-asarone enhances Gfi-1 expression, downregulates CTGF and HMGB1, and restores gemcitabine sensitivity by reducing TGF-β1 secretion from TAMs. α-Asarone can effectively reverse gemcitabine resistance in pancreatic cancer by reducing TGF-β1 secretion from TAMs, upregulating Gfi-1, and downregulating resistance factors such as CTGF and HMGB1. This restoration of gemcitabine sensitivity may improve the therapeutic efficacy of gemcitabine in pancreatic cancer treatment.

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来源期刊
Anti-Cancer Drugs
Anti-Cancer Drugs 医学-药学
CiteScore
3.80
自引率
0.00%
发文量
244
审稿时长
3 months
期刊介绍: Anti-Cancer Drugs reports both clinical and experimental results related to anti-cancer drugs, and welcomes contributions on anti-cancer drug design, drug delivery, pharmacology, hormonal and biological modalities and chemotherapy evaluation. An internationally refereed journal devoted to the fast publication of innovative investigations on therapeutic agents against cancer, Anti-Cancer Drugs aims to stimulate and report research on both toxic and non-toxic anti-cancer agents. Consequently, the scope on the journal will cover both conventional cytotoxic chemotherapy and hormonal or biological response modalities such as interleukins and immunotherapy. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool.
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