摘要
Momordica antiviral protein 30 kD(MAP30)is a type I ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To increase its tumor-targeting ability,the arginine-glycine-aspartic(RGD)peptide and the epidermal growth factor receptor interference(EGFRi)peptide were fused with MAP30,which was named ELRL-MAP30.The efficiency of targeted therapy for triple-negative breast cancer(TNBC)MDA-MB-231 cells,which lack the expression of estrogen receptor(ER),Progesterone receptor(PgR)and human epidermal growth factor receptor-2(HER2),is limited.In this study,we focus on exploring the effect and mechanism of ELRL-MAP30 on TNBC MDA-MB-231 cells.First,we discovered that ELRL-MAP30 significantly inhibited the migration and invasion of MDA-MB-231 cells and induced MDA-MB-231 cell apoptosis.Moreover,ELRL-MAP30 treatment resulted in a significant increase in Bax expression and a decrease in Bcl-2 expression.Furthermore,ELRL-MAP30 triggered apoptosis via the Fak/EGFR/Erk and Ilk/Akt signaling pathways.In addition,recombinant ELRL-MAP30 can inhibit chicken embryonic angiogenesis,and also inhibit the tube formation ability of human umbilical vein endothelial cells(HUVECs),indicating its potential therapeutic effects on tumor angiogenesis.Collectively,these results indicate that ELRL-MAP30 has significant tumor-targeting properties in MDA-MB-231 cancer cells and reveals potential therapeutic effects on angiogenesis.These findings indicate the potential role of ELRL-MAP30 in the targeted treatment of the TNBC cell line MDA-MB-231.
苦瓜抗病毒蛋白(momordica antiviral protein,MAP30)是一种大小为30 kD的I型核糖体失活蛋白质(ribosome-inactivating protein,RIP),具有抗菌、抗HIV和抗肿瘤活性,但缺乏对肿瘤细胞的靶向性。为了增加其肿瘤靶向性,将精氨酸-甘氨酸-天冬氨酸肽(arginine-glycine-aspartic peptide,RGD)和表皮生长因子受体干扰肽(epidermal growth factor receptor interference peptide,EGFRi)与MAP30融合,命名为ELRL-MAP30。缺乏雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PgR)和人表皮生长因子受体-2 (human epidermal growth factor receptor-2,HER2)表达的三阴性乳腺癌(triple-negative breast cancer,TNBC) MDA-MB-231细胞由于缺乏靶向性而在临床治疗中受到限制。本研究主要探讨ELRL-MAP30对 MDA-MB-231细胞的靶向作用及其机制。首先,我们发现ELRL-MAP30能显著抑制MDA-MB-231细胞的迁移和侵袭,并诱导MDA-MB-231细胞凋亡。ELRL-MAP30处理后显著降低Bcl-2在蛋白质的表达水平,而BAX蛋白的表达水平增加。同时,ELRL-MAP30通过Fak / EGFR / Erk和Ilk / Akt信号通路诱导细胞凋亡。此外,重组ELRL-MAP30还可以抑制鸡胚血管生成,并且抑制HUVECs细胞的成管能力,表明其对肿瘤血管生成具有潜在的治疗作用。总之,这些结果表明,ELRL-MAP30在针对三阴性乳腺癌MDA-MB-231细胞中具有显著的肿瘤靶向性,并显示出对血管生成的潜在治疗作用。这些研究表明,ELRL-MAP30在靶向治疗TNBC细胞MDA-MB-231中具有潜在作用。
出处
《中国生物化学与分子生物学报》
北大核心
2025年第2期260-272,共13页
Chinese Journal of Biochemistry and Molecular Biology
基金
浙江省大学生科技创新活动计划(No.2024R410A050)
浙江中医药大学科研基金(No.2024GJYY15)资助。
