Haixin Zhu, Minmin Shen, Yiqian Zhu, Ruoqi Wang, Rong Dong, Yuyu Huang, Lulin Zhu, Ying Li, Youyou Yan, Jiang Lou, Bo Zhang, Nengming Lin, Biqin Tan
{"title":"AZD5153在体外和体内增强吉西他滨对胰腺癌细胞的化疗敏感性。","authors":"Haixin Zhu, Minmin Shen, Yiqian Zhu, Ruoqi Wang, Rong Dong, Yuyu Huang, Lulin Zhu, Ying Li, Youyou Yan, Jiang Lou, Bo Zhang, Nengming Lin, Biqin Tan","doi":"10.1186/s12935-025-03952-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer is a malignant disease with a poor prognosis. Gemcitabine (GEM), the first-line treatment drug, shows limited efficacy because of the notorious drug resistance of pancreatic cancer. Therefore, the development of sensitive drugs for pancreatic cancer is essential. AZD5153 is a novel bivalent BET bromodomain inhibitor with multiple anti-tumor effects on malignancy. Here, we aimed to investigate the effect of AZD5153 on the GEM sensitivity in human pancreatic cancer cells.</p><p><strong>Methods: </strong>Sulforhodamine B (SRB), clone formation assays were designed to characterize the cell viability and clone formation after treatment with AZD5153 and/or GEM. DAPI staining, flow cytometry and western blotting were used to identify the cell apoptosis. RNA-seq analysis, western blotting and qPCR were also conducted to confirm the signaling pathway involved in it. Nude mice bearing PANC-1 pancreatic cancer xenograft model was conducted to confirm the combination effect of GEM and AZD5153 in vivo.</p><p><strong>Results: </strong>As a result, AZD5153 presented a strong anti-proliferation activity and exerted synergistic effects when combined with GEM in BXPC3 and PANC-1 cell lines.Meanwhile, the combination treatment also inhibited colony formation in these two cell lines. Additionally, AZD5153 combined with GEM induced cell apoptosis. Further investigations revealed that the combination of AZD5153 and GEM decreased the phosphorylation of ERK/mTOR signaling proteins, the specific chemical activators PDBu (activator of ERK) reversed the expression of c-PARP. Besides, the expression of MUC2 was remarkable decreased after combination treatment.</p><p><strong>Conclusion: </strong>In conclusion, these results suggested that AZD5153 might be an excellent GEM sensitizer in pancreatic cancer.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"315"},"PeriodicalIF":6.0000,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379372/pdf/","citationCount":"0","resultStr":"{\"title\":\"AZD5153 enhances the chemo-sensitivity of gemcitabine on pancreatic cancer cells in vitro and in vivo.\",\"authors\":\"Haixin Zhu, Minmin Shen, Yiqian Zhu, Ruoqi Wang, Rong Dong, Yuyu Huang, Lulin Zhu, Ying Li, Youyou Yan, Jiang Lou, Bo Zhang, Nengming Lin, Biqin Tan\",\"doi\":\"10.1186/s12935-025-03952-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Pancreatic cancer is a malignant disease with a poor prognosis. Gemcitabine (GEM), the first-line treatment drug, shows limited efficacy because of the notorious drug resistance of pancreatic cancer. Therefore, the development of sensitive drugs for pancreatic cancer is essential. AZD5153 is a novel bivalent BET bromodomain inhibitor with multiple anti-tumor effects on malignancy. Here, we aimed to investigate the effect of AZD5153 on the GEM sensitivity in human pancreatic cancer cells.</p><p><strong>Methods: </strong>Sulforhodamine B (SRB), clone formation assays were designed to characterize the cell viability and clone formation after treatment with AZD5153 and/or GEM. DAPI staining, flow cytometry and western blotting were used to identify the cell apoptosis. RNA-seq analysis, western blotting and qPCR were also conducted to confirm the signaling pathway involved in it. Nude mice bearing PANC-1 pancreatic cancer xenograft model was conducted to confirm the combination effect of GEM and AZD5153 in vivo.</p><p><strong>Results: </strong>As a result, AZD5153 presented a strong anti-proliferation activity and exerted synergistic effects when combined with GEM in BXPC3 and PANC-1 cell lines.Meanwhile, the combination treatment also inhibited colony formation in these two cell lines. Additionally, AZD5153 combined with GEM induced cell apoptosis. Further investigations revealed that the combination of AZD5153 and GEM decreased the phosphorylation of ERK/mTOR signaling proteins, the specific chemical activators PDBu (activator of ERK) reversed the expression of c-PARP. Besides, the expression of MUC2 was remarkable decreased after combination treatment.</p><p><strong>Conclusion: </strong>In conclusion, these results suggested that AZD5153 might be an excellent GEM sensitizer in pancreatic cancer.</p>\",\"PeriodicalId\":9385,\"journal\":{\"name\":\"Cancer Cell International\",\"volume\":\"25 1\",\"pages\":\"315\"},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2025-08-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379372/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Cell International\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12935-025-03952-2\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12935-025-03952-2","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
AZD5153 enhances the chemo-sensitivity of gemcitabine on pancreatic cancer cells in vitro and in vivo.
Background: Pancreatic cancer is a malignant disease with a poor prognosis. Gemcitabine (GEM), the first-line treatment drug, shows limited efficacy because of the notorious drug resistance of pancreatic cancer. Therefore, the development of sensitive drugs for pancreatic cancer is essential. AZD5153 is a novel bivalent BET bromodomain inhibitor with multiple anti-tumor effects on malignancy. Here, we aimed to investigate the effect of AZD5153 on the GEM sensitivity in human pancreatic cancer cells.
Methods: Sulforhodamine B (SRB), clone formation assays were designed to characterize the cell viability and clone formation after treatment with AZD5153 and/or GEM. DAPI staining, flow cytometry and western blotting were used to identify the cell apoptosis. RNA-seq analysis, western blotting and qPCR were also conducted to confirm the signaling pathway involved in it. Nude mice bearing PANC-1 pancreatic cancer xenograft model was conducted to confirm the combination effect of GEM and AZD5153 in vivo.
Results: As a result, AZD5153 presented a strong anti-proliferation activity and exerted synergistic effects when combined with GEM in BXPC3 and PANC-1 cell lines.Meanwhile, the combination treatment also inhibited colony formation in these two cell lines. Additionally, AZD5153 combined with GEM induced cell apoptosis. Further investigations revealed that the combination of AZD5153 and GEM decreased the phosphorylation of ERK/mTOR signaling proteins, the specific chemical activators PDBu (activator of ERK) reversed the expression of c-PARP. Besides, the expression of MUC2 was remarkable decreased after combination treatment.
Conclusion: In conclusion, these results suggested that AZD5153 might be an excellent GEM sensitizer in pancreatic cancer.
期刊介绍：
Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques.
The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors.
Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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