{"title":"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","authors":"Jiaqi Yu, Yuzhe Xue, Zhaofeng Gao, Lingyu Hu, Xiaorong Liu, Xuesong He, Xiaoguang Wang","doi":"10.1097/CAD.0000000000001740","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"664-674"},"PeriodicalIF":2.2000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329808/pdf/","citationCount":"0","resultStr":"{\"title\":\"α-Asarone attenuates tumor-associated macrophages-induced gemcitabine resistance in pancreatic carcinoma via the transforming growth factor-beta 1/growth factor independent 1 axis.\",\"authors\":\"Jiaqi Yu, Yuzhe Xue, Zhaofeng Gao, Lingyu Hu, Xiaorong Liu, Xuesong He, Xiaoguang Wang\",\"doi\":\"10.1097/CAD.0000000000001740\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":7969,\"journal\":{\"name\":\"Anti-Cancer Drugs\",\"volume\":\" \",\"pages\":\"664-674\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329808/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Anti-Cancer Drugs\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/CAD.0000000000001740\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/6/13 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Anti-Cancer Drugs","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/CAD.0000000000001740","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/13 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
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.
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.