Aims

Increased expression of inhibitor of apoptosis (IAP) genes has been associated with progressive cancer and chemoresistance. Accordingly, blockade of IAPs by BV6 has resulted in ameliorative outcomes. Interleukin (IL)-6 is another important mediator involved in the growth and survival of tumor cells. Therefore, we hypothesized that simultaneous inhibition of IAPs and IL-6 could be a new promising anti-tumor treatment strategy.

Materials and methods

In this study, we generated and characterized hyaluronate-PEG-Chitosan-Lactate (H-PCL) nanoparticles (NPs) to simultaneously deliver IL6-specific siRNA and BV6 to 4T1 (breast cancer) and CT26 (colon cancer) cells, and investigate the anti-tumor properties of this combination therapy both in vitro and in vivo.

Key findings

H-PCL NPs exhibited good physicochemical properties leading to efficient transfection of cancer cells and suppression of target molecules. Moreover, combination therapy synergistically increased apoptosis, as well as decreased cell migration, proliferation, colony formation, and angiogenesis in both 4T1 and CT26 cell lines and suppressed cancer progression in tumor-bearing mice that was associated with enhanced survival time.

Significance

These findings imply the effectiveness of cancer combination therapy by using H-PCL NPs loaded with anti-IL-6 siRNA and BV6.

中文翻译：

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撤回：通过透明质酸缀合的 PEG-壳聚糖-乳酸盐纳米颗粒同时递送 BV6 和抗 IL6 siRNA 可抑制肿瘤进展

 目标

凋亡抑制剂 (IAP) 基因表达的增加与进展性癌症和化疗耐药有关。因此，BV6 对 IAP 的阻断带来了改善的结果。白细胞介素 (IL)-6 是参与肿瘤细胞生长和存活的另一种重要介质。因此，我们假设同时抑制 IAP 和 IL-6 可能是一种新的有前景的抗肿瘤治疗策略。

 材料和方法

在本研究中，我们生成并表征了透明质酸-PEG-壳聚糖-乳酸盐 (H-PCL) 纳米粒子 (NP)，以同时将 IL6 特异性 siRNA 和 BV6 递送至 4T1（乳腺癌）和 CT26（结肠癌）细胞，并研究了这种联合疗法在体外和体内的抗肿瘤特性。

 主要发现

H-PCL NPs 表现出良好的理化特性，可有效转染癌细胞并抑制靶分子。此外，联合治疗可协同增加 4T1 和 CT26 细胞系的细胞凋亡，并减少细胞迁移、增殖、集落形成和血管生成，并抑制荷瘤小鼠的癌症进展，从而延长生存时间。

 意义

这些发现表明使用负载抗 IL-6 siRNA 和 BV6 的 H-PCL NP 进行癌症联合治疗是有效的。