Amjadi Issa, Mohajeri Mohammad, Borisov Andrei, Hosseini Motahare-Sadat
Department of Biomedical Engineering, Wayne State University, Detroit, United States.
Department of Medical Biotechnology, Mashhad University of Medical Sciences, Mashhad, Iran.
J Pharmacopuncture. 2019 Jun;22(2):102-108. doi: 10.3831/KPI.2019.22.013. Epub 2019 Jun 30.
Esophageal squamous cell carcinoma (ESCC) is considered as a deadly medical condition that affects a growing number of people worldwide. Targeted therapy of ESCC has been suggested recently and required extensive research. With cyclin D1 as a therapeutic target, the present study aimed at evaluating the anticancer effects of doxorubicin (Dox) or L. (HP) extract encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles on the ESCC cell line KYSE30.
Nanoparticles were prepared using double emulsion method. Cytotoxicity assay was carried out to measure the anti-proliferation activity of Dox-loaded (Dox NPs) and HP-loaded nanoparticles (HP NPs) against both cancer and normal cell lines. The mRNA gene expression of cyclin D1 was evaluated to validate the cytotoxicity studies at molecular level.
Free drugs and nanoparticles significantly inhibited KYSE30 cells by 55-73% and slightly affected normal cells up to 29%. The IC of Dox NPs and HP NPs was ~ 0.04-0.06 mg/mL and ~ 0.6-0.7 mg/mL, respectively. Significant decrease occurred in cyclin D1 expression by Dox NPs and HP NPs (P < 0.05). Exposure of KYSE-30 cells to combined treatments including both Dox and HP extract significantly increased the level of cyclin D1 expression as compared to those with individual treatments (P < 0.05).
Dox NPs and HP NPs can successfully and specifically target ESCC cells through downregulation of cyclin D1. The simultaneous use of Dox and HP extract should be avoided for the treatment of ESCC.
食管鳞状细胞癌（ESCC）被认为是一种致命的疾病，在全球影响着越来越多的人。最近有人提出对ESCC进行靶向治疗，这需要广泛的研究。本研究以细胞周期蛋白D1为治疗靶点，旨在评估包裹在聚乳酸-乙醇酸共聚物（PLGA）纳米颗粒中的阿霉素（Dox）或幽门螺杆菌（HP）提取物对ESCC细胞系KYSE30的抗癌作用。
采用双乳液法制备纳米颗粒。进行细胞毒性试验以测量载有Dox的纳米颗粒（Dox NPs）和载有HP的纳米颗粒（HP NPs）对癌细胞系和正常细胞系的抗增殖活性。评估细胞周期蛋白D1的mRNA基因表达，以在分子水平验证细胞毒性研究。
游离药物和纳米颗粒显著抑制KYSE30细胞达55%-73%，对正常细胞的影响轻微，最高达29%。Dox NPs和HP NPs的半数抑制浓度（IC）分别约为0.04-0.06 mg/mL和0.6-0.7 mg/mL。Dox NPs和HP NPs使细胞周期蛋白D1表达显著降低（P<0.05）。与单独治疗相比，KYSE-30细胞暴露于包括Dox和HP提取物的联合治疗中，细胞周期蛋白D1表达水平显著升高（P<0.05）。
Dox NPs和HP NPs可通过下调细胞周期蛋白D1成功且特异性地靶向ESCC细胞。治疗ESCC时应避免同时使用Dox和HP提取物。
