{"title":"芍药苷通过抑制Cyr61的产生使耐伊马替尼甲磺酸慢性髓系白血病细胞增敏。","authors":"Yanfang Song, Li Luo, Zhen Lin, Taigang Zhang, Zhaozhong Li, Yinping Cao, Xianjin Zhu","doi":"10.1097/CAD.0000000000001681","DOIUrl":null,"url":null,"abstract":"<p><p>Imatinib mesylate (IM) is a first-line therapy for chronic myeloid leukemia (CML) and exhibits good therapeutic effects, but not in all patients with CML owing to drug resistance. Our previous study showed that Cyr61 plays a key role in IM resistance in CML cells. Paeoniflorin (PF) is a bioactive compound isolated from the traditional Chinese medicine Paeonia lactiflora Pall that displays anticancer activity. Little is, however, known regarding the role of PF in IM-resistant CML cells. This study aimed to evaluate whether PF could decrease Cyr61 production and improve IM-resistant CML cell sensitivity to IM and to investigate the underlying mechanisms. CML cell lines (K562 and KCL22) and IM-resistant cell lines (K562G and KCL22R) were used as CML study models. Cyr61 expression was assessed in both parental and IM-resistant CML cells by western blotting, real-time quantitative PCR , and ELISA. Lentiviral vectors were used to induce the knockdown of Cyr61 expression, followed by a comprehensive evaluation of cell proliferation and apoptosis. The results showed that PF decreased the production of Cyr61 in the presence of IM by inhibiting extracellular regulated protein kinases 1/2 activation. PF significantly decreased the IC50 value of IM and increased IM-induced apoptosis of IM-resistant CML cells. Importantly, PF also improved the sensitivity of CML cells to bosutinib and dasatinib via inhibition of Cyr61 production. In conclusion, we report for the first time that PF may effectively improve the sensitivity of IM-resistant CML cells to IM, bosutinib, and dasatinib, at least in part, by subsequently downregulating Cyr61.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"190-198"},"PeriodicalIF":1.8000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Paeoniflorin sensitizes imatinib mesylate-resistant chronic myeloid leukemia cells via the inhibition of Cyr61 production.\",\"authors\":\"Yanfang Song, Li Luo, Zhen Lin, Taigang Zhang, Zhaozhong Li, Yinping Cao, Xianjin Zhu\",\"doi\":\"10.1097/CAD.0000000000001681\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Imatinib mesylate (IM) is a first-line therapy for chronic myeloid leukemia (CML) and exhibits good therapeutic effects, but not in all patients with CML owing to drug resistance. Our previous study showed that Cyr61 plays a key role in IM resistance in CML cells. Paeoniflorin (PF) is a bioactive compound isolated from the traditional Chinese medicine Paeonia lactiflora Pall that displays anticancer activity. Little is, however, known regarding the role of PF in IM-resistant CML cells. This study aimed to evaluate whether PF could decrease Cyr61 production and improve IM-resistant CML cell sensitivity to IM and to investigate the underlying mechanisms. CML cell lines (K562 and KCL22) and IM-resistant cell lines (K562G and KCL22R) were used as CML study models. Cyr61 expression was assessed in both parental and IM-resistant CML cells by western blotting, real-time quantitative PCR , and ELISA. Lentiviral vectors were used to induce the knockdown of Cyr61 expression, followed by a comprehensive evaluation of cell proliferation and apoptosis. The results showed that PF decreased the production of Cyr61 in the presence of IM by inhibiting extracellular regulated protein kinases 1/2 activation. PF significantly decreased the IC50 value of IM and increased IM-induced apoptosis of IM-resistant CML cells. Importantly, PF also improved the sensitivity of CML cells to bosutinib and dasatinib via inhibition of Cyr61 production. In conclusion, we report for the first time that PF may effectively improve the sensitivity of IM-resistant CML cells to IM, bosutinib, and dasatinib, at least in part, by subsequently downregulating Cyr61.</p>\",\"PeriodicalId\":7969,\"journal\":{\"name\":\"Anti-Cancer Drugs\",\"volume\":\" \",\"pages\":\"190-198\"},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2025-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Anti-Cancer Drugs\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/CAD.0000000000001681\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/7 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.0000000000001681","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/7 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
Paeoniflorin sensitizes imatinib mesylate-resistant chronic myeloid leukemia cells via the inhibition of Cyr61 production.
Imatinib mesylate (IM) is a first-line therapy for chronic myeloid leukemia (CML) and exhibits good therapeutic effects, but not in all patients with CML owing to drug resistance. Our previous study showed that Cyr61 plays a key role in IM resistance in CML cells. Paeoniflorin (PF) is a bioactive compound isolated from the traditional Chinese medicine Paeonia lactiflora Pall that displays anticancer activity. Little is, however, known regarding the role of PF in IM-resistant CML cells. This study aimed to evaluate whether PF could decrease Cyr61 production and improve IM-resistant CML cell sensitivity to IM and to investigate the underlying mechanisms. CML cell lines (K562 and KCL22) and IM-resistant cell lines (K562G and KCL22R) were used as CML study models. Cyr61 expression was assessed in both parental and IM-resistant CML cells by western blotting, real-time quantitative PCR , and ELISA. Lentiviral vectors were used to induce the knockdown of Cyr61 expression, followed by a comprehensive evaluation of cell proliferation and apoptosis. The results showed that PF decreased the production of Cyr61 in the presence of IM by inhibiting extracellular regulated protein kinases 1/2 activation. PF significantly decreased the IC50 value of IM and increased IM-induced apoptosis of IM-resistant CML cells. Importantly, PF also improved the sensitivity of CML cells to bosutinib and dasatinib via inhibition of Cyr61 production. In conclusion, we report for the first time that PF may effectively improve the sensitivity of IM-resistant CML cells to IM, bosutinib, and dasatinib, at least in part, by subsequently downregulating Cyr61.
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.