Cancer multidrug resistance(MDR)impairs the therapeutic efficacy of various chemotherapeutics.Novel approaches,particularly the development of MDR reversal agents,are critically needed to address this challenge.This s...Cancer multidrug resistance(MDR)impairs the therapeutic efficacy of various chemotherapeutics.Novel approaches,particularly the development of MDR reversal agents,are critically needed to address this challenge.This study demonstrates that tenacissoside I(TI),a compound isolated from Marsdenia tenacissima(Roxb.)Wight et Arn,traditionally used in clinical practice as an ethnic medicine for cancer treatment,exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells.TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin(DOX)and paclitaxel(PAC)by downregulating ABCB1 expression and reducing ABCB1 drug transport function.Mechanistically,protein arginine methyltransferase 1(PRMT1),whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues,was differentially expressed in TI-treated SW620/AD300 cells.SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine(aDMA)and enhanced PRMT1-EGFR interaction compared to their parental cells.Moreover,TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR,PRMT1-EGFR interaction,and EGFR downstream signaling in SW620/AD300 and KBV200 cells.These effects were significantly reversed by PRMT1 overexpression.Additionally,TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities.This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR,suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.展开更多
2025年4月5日,上海交通大学医学院附属新华医院检验科郑英霞教授团队在权威期刊Journal for Immunotherapy of Cancer发表题目为“PRMT5 deficiency in myeloid cells reprograms macrophages to enhance antitumor immunity and synerg...2025年4月5日,上海交通大学医学院附属新华医院检验科郑英霞教授团队在权威期刊Journal for Immunotherapy of Cancer发表题目为“PRMT5 deficiency in myeloid cells reprograms macrophages to enhance antitumor immunity and synergizes with anti-PD-L1 therapy”的研究论文。该研究揭示了蛋白精氨酸甲基转移酶5(protein arginine methyltransferase 5,PRMT5)通过STAT6-PPARγ途径调节脂质代谢,促进单核巨噬细胞的迁移和分化,促进巨噬细胞向M2型极化。在小鼠髓系细胞中特异性敲除Prmt5(Prmt5 cKO)并进行肿瘤模型构建,发现在敲除鼠中肿瘤相关巨噬细胞发生重编程,抗肿瘤活性增强,抑制肿瘤进展并显著增强抗程序性死亡受体配体1(programmed death-ligand 1,PD-L1)的免疫治疗效果。该研究结果提示靶向髓系细胞中的PRMT5有望为癌症免疫治疗提供一种新的方法。展开更多
[Objective] The aim of experiment was to lay molecular foundation for studying maturity mechanism of banana after harvest. [Method] The combined method of suppressing subtractive hybridization and cDNA micro-array wer...[Objective] The aim of experiment was to lay molecular foundation for studying maturity mechanism of banana after harvest. [Method] The combined method of suppressing subtractive hybridization and cDNA micro-array were used to obtain cDNA segment of one PRMT gene in banana and the whole cDNA sequence of the gene was cloned.The bioinformatics analysis was operated on it,in addition, the expression profile analysis was conducted in different organs and different mature periods of banana.[Result] The whole length of cDNA in MaPRMT1 was 1 158 bp and possessed a complete open reading frame,which could encode 385 amino acids.It had high homology with PRMT in plant,containing one Methyltransf_1 domain.The MaPRMT1 gene was expressed in root,stem,leaf and fruit of banana and the expression levels in stem and leaf were relatively high.As the increase of days after harvest,the expression level declined gradually,however it reached maximum when ethylene release was biggest,then it declined.[Conclusion] MaPRMT1 belonged to the first kind of arginine methyltransferase and it was expressed differently in different organs and fruits at different mature periods.展开更多
目的构建精氨酸甲基转移酶2(PRMT2)慢病毒表达载体。方法通过PCR扩增PRMT2 c DNA,将PRMT2 c DNA连接于GV308载体,经测序确认后,将GV308/PRMT2与p Helper 1.0和p Helper 2.0共转染至293T细胞中,收获病毒,通过Real time PCR测定滴度;将PR...目的构建精氨酸甲基转移酶2(PRMT2)慢病毒表达载体。方法通过PCR扩增PRMT2 c DNA,将PRMT2 c DNA连接于GV308载体,经测序确认后,将GV308/PRMT2与p Helper 1.0和p Helper 2.0共转染至293T细胞中,收获病毒,通过Real time PCR测定滴度;将PRMT2慢病毒表达载体侵染293T细胞,通过四环素诱导和Western blot检测PRMT2慢病毒表达载体的表达能力。结果在感染PRMT2慢病毒载体293T细胞中能检测到PRMT2-3Flag融合蛋白的表达。结论成功构建PRMT2的慢病毒表达载体。展开更多
基金supported by the National Natural Science Foundation of China(Nos.82274211 and 82474190)the Natural Science Foundation of Tianjin(Nos.24JCZDJC00120 and 24PTLYHZ00280)Liaoning Provincial Department of Education Basic Research Projects for Higher Education Institutions(No.LJ212510163021)。
文摘Cancer multidrug resistance(MDR)impairs the therapeutic efficacy of various chemotherapeutics.Novel approaches,particularly the development of MDR reversal agents,are critically needed to address this challenge.This study demonstrates that tenacissoside I(TI),a compound isolated from Marsdenia tenacissima(Roxb.)Wight et Arn,traditionally used in clinical practice as an ethnic medicine for cancer treatment,exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells.TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin(DOX)and paclitaxel(PAC)by downregulating ABCB1 expression and reducing ABCB1 drug transport function.Mechanistically,protein arginine methyltransferase 1(PRMT1),whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues,was differentially expressed in TI-treated SW620/AD300 cells.SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine(aDMA)and enhanced PRMT1-EGFR interaction compared to their parental cells.Moreover,TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR,PRMT1-EGFR interaction,and EGFR downstream signaling in SW620/AD300 and KBV200 cells.These effects were significantly reversed by PRMT1 overexpression.Additionally,TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities.This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR,suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
文摘2025年4月5日,上海交通大学医学院附属新华医院检验科郑英霞教授团队在权威期刊Journal for Immunotherapy of Cancer发表题目为“PRMT5 deficiency in myeloid cells reprograms macrophages to enhance antitumor immunity and synergizes with anti-PD-L1 therapy”的研究论文。该研究揭示了蛋白精氨酸甲基转移酶5(protein arginine methyltransferase 5,PRMT5)通过STAT6-PPARγ途径调节脂质代谢,促进单核巨噬细胞的迁移和分化,促进巨噬细胞向M2型极化。在小鼠髓系细胞中特异性敲除Prmt5(Prmt5 cKO)并进行肿瘤模型构建,发现在敲除鼠中肿瘤相关巨噬细胞发生重编程,抗肿瘤活性增强,抑制肿瘤进展并显著增强抗程序性死亡受体配体1(programmed death-ligand 1,PD-L1)的免疫治疗效果。该研究结果提示靶向髓系细胞中的PRMT5有望为癌症免疫治疗提供一种新的方法。
文摘[Objective] The aim of experiment was to lay molecular foundation for studying maturity mechanism of banana after harvest. [Method] The combined method of suppressing subtractive hybridization and cDNA micro-array were used to obtain cDNA segment of one PRMT gene in banana and the whole cDNA sequence of the gene was cloned.The bioinformatics analysis was operated on it,in addition, the expression profile analysis was conducted in different organs and different mature periods of banana.[Result] The whole length of cDNA in MaPRMT1 was 1 158 bp and possessed a complete open reading frame,which could encode 385 amino acids.It had high homology with PRMT in plant,containing one Methyltransf_1 domain.The MaPRMT1 gene was expressed in root,stem,leaf and fruit of banana and the expression levels in stem and leaf were relatively high.As the increase of days after harvest,the expression level declined gradually,however it reached maximum when ethylene release was biggest,then it declined.[Conclusion] MaPRMT1 belonged to the first kind of arginine methyltransferase and it was expressed differently in different organs and fruits at different mature periods.
文摘目的构建精氨酸甲基转移酶2(PRMT2)慢病毒表达载体。方法通过PCR扩增PRMT2 c DNA,将PRMT2 c DNA连接于GV308载体,经测序确认后,将GV308/PRMT2与p Helper 1.0和p Helper 2.0共转染至293T细胞中,收获病毒,通过Real time PCR测定滴度;将PRMT2慢病毒表达载体侵染293T细胞,通过四环素诱导和Western blot检测PRMT2慢病毒表达载体的表达能力。结果在感染PRMT2慢病毒载体293T细胞中能检测到PRMT2-3Flag融合蛋白的表达。结论成功构建PRMT2的慢病毒表达载体。
