a Department of Pharmaceutics, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
b School of Pharmacy, International Campus , Iran University of Medical Sciences , Tehran , Iran.
Drug Dev Ind Pharm. 2018 Sep;44(9):1434-1442. doi: 10.1080/03639045.2018.1459674. Epub 2018 May 2.
Recently, salinomycin (SAL) has been reported to inhibit proliferation and induce apoptosis in various tumors. The aim of this study was to deliver SAL to orthotopic model of pancreatic cancer by the aid of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs).
The NPs were physico-chemically characterized and evaluated for cytotoxicity on luciferase-transduced AsPC-1 cells in vitro as well as implanted orthotopically into the pancreas of nude mice.
SAL (3.5 mg/kg every other day) blocked tumor growth by 52% compared to the control group after 3 weeks of therapy. Western blotting of tumor protein extracts indicated that SAL treatment leads to up-regulation of E-cadherin, β-catenin, and transforming growth factor beta receptor (TGFβR) expressions in AsPC-1 orthotopic tumor. Noteworthy, immunofluorescence staining of adjacent tumor sections showed that treatment with SAL NPs cause significant apoptosis in the tumor cells rather than the stroma. Further investigations also revealed that TGFβR2 over-expression was induced in stroma cells after treatment with SAL NPs.
These results highlight SAL-loaded PLGA NPs as a promising system for pancreatic cancer treatment, while the mechanistic questions need to be subsequently tested.
最近有报道称，萨利霉素（SAL）可抑制多种肿瘤的增殖并诱导其凋亡。本研究旨在通过聚乳酸-羟基乙酸共聚物（PLGA）纳米粒（NPs）将 SAL 递送至胰腺癌原位模型。
对 NPs 进行物理化学特性表征，并在体外对转染荧光素酶的 AsPC-1 细胞进行细胞毒性评估，以及将其植入裸鼠胰腺原位。
与对照组相比，SAL（3.5mg/kg，每隔一天一次）治疗 3 周后可使肿瘤生长抑制 52%。肿瘤蛋白提取物的 Western blot 分析表明，SAL 处理导致 AsPC-1 原位肿瘤中 E-钙黏蛋白、β-连环蛋白和转化生长因子β受体（TGFβR）的表达上调。值得注意的是，SAL NPs 治疗后的相邻肿瘤切片免疫荧光染色显示，SAL NPs 治疗可导致肿瘤细胞而非基质发生明显凋亡。进一步的研究还表明，SAL NPs 治疗后基质细胞中 TGFβR2 的过表达。
这些结果强调了负载 SAL 的 PLGA NPs 作为一种有前途的胰腺癌治疗系统，而机制问题需要进一步测试。
