Tu Lin, Wang Ming, Zhao Wen-Yi, Zhang Zi-Zhen, Tang De-Feng, Zhang Ye-Qian, Cao Hui, Zhang Zhi-Gang
Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China.
Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China.
Mater Sci Eng C Mater Biol Appl. 2017 Mar 1;72:177-184. doi: 10.1016/j.msec.2016.10.052. Epub 2016 Oct 26.
Gastrointestinal stromal tumors (GIST) are one of the most common forms of mesenchymal cancers of the gastrointestinal tract. Although chemotherapeutic drugs inhibited the proliferation of GIST, however, sizable proportion of people developed resistance and therefore difficult to treat. In the present study, O-carboxymethyl chitosan (OCMC)-tocopherol polymer conjugate was synthesized and formulated into stable polymeric nanoparticles. The main aim of present study was to increase the therapeutic efficacy of miR-218 in GIST. The mean size of nanoparticles was ~110nm with a spherical shape. The miR-218 NP has been shown inhibit the cell proliferation and exhibited a superior cell apoptosis. The miR-218 NP inhibited the cell invasion and promoted the apoptosis of GIST cancer cells. In the present study, we have successfully showed that KIT1 is the target gene of miR-218 as shown by the luciferase reporter assay. These findings collectively suggest the miR-218 loaded nanoparticle by virtue of effective transfection could act as a tumor suppressor miRNA in the treatment of GIST.
胃肠道间质瘤（GIST）是胃肠道间充质癌最常见的形式之一。尽管化疗药物可抑制GIST的增殖，然而，相当一部分人会产生耐药性，因此难以治疗。在本研究中，合成了O-羧甲基壳聚糖（OCMC）-生育酚聚合物共轭物，并将其制成稳定的聚合物纳米颗粒。本研究的主要目的是提高miR-218在GIST中的治疗效果。纳米颗粒的平均尺寸约为110nm，呈球形。已证明miR-218纳米颗粒可抑制细胞增殖并表现出卓越的细胞凋亡作用。miR-218纳米颗粒抑制细胞侵袭并促进GIST癌细胞凋亡。在本研究中，荧光素酶报告基因检测表明，我们已成功证明KIT1是miR-218的靶基因。这些发现共同表明，负载miR-218的纳米颗粒凭借有效的转染可作为一种肿瘤抑制性miRNA用于GIST的治疗。
