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Regulating the Golgi apparatus by co-delivery of a COX-2 inhibitor and Brefeldin A for suppression of tumor metastasis†
Biomaterials Science ( IF 5.8 ) Pub Date : 2018-06-06 00:00:00 , DOI: 10.1039/c8bm00381e Ru-Yi Yu 1, 2, 3, 4, 5 , Lei Xing 1, 2, 3, 4, 5 , Peng-Fei Cui 1, 2, 3, 4, 5 , Jian-Bin Qiao 1, 2, 3, 4, 5 , Yu-Jing He 1, 2, 3, 4, 5 , Xin Chang 1, 2, 3, 4, 5 , Tian-Jiao Zhou 1, 2, 3, 4, 5 , Qing-Ri Jin 5, 6, 7, 8 , Hu-Lin Jiang 1, 2, 3, 4, 5 , Yanyu Xiao 1, 2, 3, 4, 5
Biomaterials Science ( IF 5.8 ) Pub Date : 2018-06-06 00:00:00 , DOI: 10.1039/c8bm00381e Ru-Yi Yu 1, 2, 3, 4, 5 , Lei Xing 1, 2, 3, 4, 5 , Peng-Fei Cui 1, 2, 3, 4, 5 , Jian-Bin Qiao 1, 2, 3, 4, 5 , Yu-Jing He 1, 2, 3, 4, 5 , Xin Chang 1, 2, 3, 4, 5 , Tian-Jiao Zhou 1, 2, 3, 4, 5 , Qing-Ri Jin 5, 6, 7, 8 , Hu-Lin Jiang 1, 2, 3, 4, 5 , Yanyu Xiao 1, 2, 3, 4, 5
Affiliation
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Finding a cure for breast cancer currently remains a medical challenge in due to the failure of common treatment methods to inhibit invasion and metastasis of cancer cells, which eventually leads to recurrence of breast cancer. Many secreted proteins are overexpressed and play crucial roles in tumorigenesis and development. The Golgi apparatus is a key protein processing and secretion factory in which metastasis-associated proteins are modified, transported and secreted; thus, regulating the Golgi apparatus of tumor cells is a viable strategy to inhibit tumor metastasis. Herein, celecoxib (CLX) and Brefeldin A (BFA) were encapsulated into the biocompatible polymer PLGA-PEG to form nanoparticles that act on the Golgi apparatus to treat metastatic breast cancer; CLX is a specific COX-2 inhibitor which accumulates in the Golgi apparatus, and BFA is a protein transport inhibitor fusing the Golgi apparatus into endoplasmic reticulum. The optimized CLX and BFA co-loaded nanoparticles (CBNPs) possessed good physicochemical properties. CBNPs efficiently damaged the Golgi apparatus within 30 min and showed enhanced cytotoxicity of CLX and BFA toward murine metastatic breast cancer 4T1 cells. The migration and invasion abilities of the cells were dramatically suppressed by the CBNPs. Further, the expression and secretion of metastasis-associated proteins such as matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) were remarkably decreased. Our findings showed that co-delivering CLX and BFA to regulate the Golgi apparatus may be an efficient strategy to inhibit breast cancer growth and suppress tumor cell metastasis.
中文翻译：
通过共同递送COX-2抑制剂和布雷菲德菌素A来调节高尔基体以抑制肿瘤转移†
由于常用的治疗方法不能抑制癌细胞的侵袭和转移，因此找到治疗乳腺癌的方法目前仍然是医学上的挑战，这最终导致了乳腺癌的复发。许多分泌的蛋白过表达并在肿瘤发生和发展中起关键作用。高尔基体是关键的蛋白质加工和分泌工厂，其中转移相关蛋白被修饰，运输和分泌。因此，调节肿瘤细胞的高尔基体是抑制肿瘤转移的可行策略。在此，塞来昔布（CLX）和布雷菲德菌素A（BFA）被封装到生物相容性聚合物PLGA-PEG中，形成作用于高尔基体以治疗转移性乳腺癌的纳米颗粒。CLX是一种特定的COX-2抑制剂，可在高尔基体中积累，BFA是一种蛋白质转运抑制剂，可将高尔基体融合到内质网中。优化的CLX和BFA共载纳米粒子（CBNPs）具有良好的理化性质。CBNPs在30分钟内有效损坏了高尔基体，并显示出CLX和BFA对小鼠转移性乳腺癌4T1细胞的细胞毒性增强。CBNPs显着抑制了细胞的迁移和侵袭能力。此外，与转移相关的蛋白质如基质金属蛋白酶9（MMP-9）和血管内皮生长因子（VEGF）的表达和分泌也明显减少。我们的研究结果表明，共同提供CLX和BFA来调节高尔基体可能是抑制乳腺癌生长和抑制肿瘤细胞转移的有效策略。
更新日期：2018-06-06
中文翻译：
通过共同递送COX-2抑制剂和布雷菲德菌素A来调节高尔基体以抑制肿瘤转移†
由于常用的治疗方法不能抑制癌细胞的侵袭和转移，因此找到治疗乳腺癌的方法目前仍然是医学上的挑战，这最终导致了乳腺癌的复发。许多分泌的蛋白过表达并在肿瘤发生和发展中起关键作用。高尔基体是关键的蛋白质加工和分泌工厂，其中转移相关蛋白被修饰，运输和分泌。因此，调节肿瘤细胞的高尔基体是抑制肿瘤转移的可行策略。在此，塞来昔布（CLX）和布雷菲德菌素A（BFA）被封装到生物相容性聚合物PLGA-PEG中，形成作用于高尔基体以治疗转移性乳腺癌的纳米颗粒。CLX是一种特定的COX-2抑制剂，可在高尔基体中积累，BFA是一种蛋白质转运抑制剂，可将高尔基体融合到内质网中。优化的CLX和BFA共载纳米粒子（CBNPs）具有良好的理化性质。CBNPs在30分钟内有效损坏了高尔基体，并显示出CLX和BFA对小鼠转移性乳腺癌4T1细胞的细胞毒性增强。CBNPs显着抑制了细胞的迁移和侵袭能力。此外，与转移相关的蛋白质如基质金属蛋白酶9（MMP-9）和血管内皮生长因子（VEGF）的表达和分泌也明显减少。我们的研究结果表明，共同提供CLX和BFA来调节高尔基体可能是抑制乳腺癌生长和抑制肿瘤细胞转移的有效策略。
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