龙葵活性成分澳洲茄胺靶向ABCB1克服前列腺癌细胞多西他赛耐药  

Solanum nigrum L.'s active component solasodine targets ABCB1 to overcome docetaxel resistance in prostate cancer

作　　者：邵旭龙 侯鑫妤 于涛 尚子临 罗青 林瑞惠 潘智芳 王国颖 冯卫国 SHAO Xulong;HOU Xinyu;YU Tao;SHANG Zilin;LUO Qing;LIN Ruihui;PAN Zhifang;WANG Guoying;FENG Weiguo(School of Life Science and Technology,Shandong Second Medical University,Weifang,Shandong 261053,China;School of Clinical Medicine,Shandong Second Medical University,Weifang,Shandong 261000,China;Department of Dermatology,Weifang People's Hospital,Weifang,Shandong 261000,China)

机构地区：[1]山东第二医科大学生命科学与技术学院,山东潍坊261053 [2]山东第二医科大学临床医学院,山东潍坊261000 [3]潍坊市人民医院皮肤科,山东潍坊261000

出　　处：《上海中医药杂志》2025年第5期8-14,共7页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81802905);山东省自然科学基金项目(ZR2020MH263)。

摘　　要：目的探讨龙葵的活性成分澳洲茄胺(solasodine)能否靶向ATP结合盒转运体B1(ABCB1)克服前列腺癌细胞多西他赛耐药及其作用机制。方法通过网络药理学分析龙葵的活性成分及靶基因。通过分子对接评估solasodine与ABCB1的结合情况。通过噻唑蓝(MTT)实验检测solasodine对前列腺癌细胞多西他赛耐药性的影响。通过Western blot法与免疫荧光染色法检测solasodine对ABCB1蛋白表达、亚细胞定位以及蛋白激酶B(Akt)、细胞外调节蛋白激酶(ERK)通路的影响,并通过流式细胞术检测solasodine对药物累积与外排的影响。结果网络药理学分析结果显示,solasodine对前列腺癌的治疗作用可能与ABCB1有关。分子对接结果显示,solasodine与ABCB1蛋白可以稳定结合。MTT实验结果显示,solasodine能靶向ABCB1克服前列腺癌多西他赛耐药。Westernblot法与免疫荧光染色法结果表明,solasodine不影响ABCB1在细胞内的表达与定位,也不影响Akt与ERK信号通路;流式细胞术结果显示,solasodine通过抑制ABCB1蛋白的外排功能,增加前列腺癌细胞内多西他赛的蓄积,从而克服多西他赛耐药。结论龙葵活性成分solasodine可以靶向ABCB1有效克服前列腺癌细胞多西他赛耐药。Objective To explore whether solasodine,an active component of Solanum nigrum L.,can target ATP binding cassette subfamily B member 1(ABCB1)to overcome docetaxel resistance in prostate cancer and to elucidate its mechanism of action.Methods The active components and target genes of Solanum nigrum L.were analyzed by network pharmacology.The interaction between solasodine and ABCB1 was assessed using molecular docking.The effect of solasodine on docetaxel resistance in prostate cancer cells was detected by thiazole blue(MTT)assay.The effects of solasodine on ABCB1 expression,localization,protein kinase B(Akt)and extracellular regulatory protein kinase(ERK)pathways were detected by Western blot and immunofluorescence.Additionally,the effects of solasodine on drug accumulation and efflux were detected by flow cytometry.Results Network pharmacological analysis result showed that the therapeutic effect of solasodine on prostate cancer were potentially associated with ABCB1.Molecular docking result revealed that solasodine could bind stably to ABCB1.MTT assay result demonstrated that solasodine could overcome docetaxel resistance by targeting ABCB1.Western blot and immunofluorescence results showed that solasodine did not affect ABCB1 expression and localization,nor did it affect Akt and ERK signaling pathways.Flow cytometry result showed that solasodine overcame docetaxel resistance by inhibiting ABCB1 efflux and increasing intracellular drug accumulation.Conclusion Solanum nigrum L.'s active component solasodine can target ABCB1 to effectively overcome docetaxel resistance in prostate cancer.

关 键 词：前列腺癌 龙葵 澳洲茄胺 多西他赛 耐药 网络药理学 中药研究 

分 类 号：R285[医药卫生—中药学]