Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Int J Mol Sci. 2022 Oct 21;23(20):12666. doi: 10.3390/ijms232012666.
Angiogenesis inhibitor drugs have been explored as important pharmacological agents for cancer therapy, including hepatocellular carcinoma. These agents have several drawbacks, such as drug resistance, nonspecific toxicity, and systemic side effects. Therefore, combination therapy of the drug and small interfering RNA could be a promising option to achieve high therapeutic efficacy while allowing a lower systemic dose. Therefore, we studied adding an alpha-fetoprotein siRNA (-siRNA) incorporated on polymeric nanoparticles (NPs) along with angiogenesis inhibitor drugs. The siRNA-loaded NPs were successfully synthesized at an average size of 242.00 ± 2.54 nm. Combination treatment of -siRNA NPs and a low dose of sunitinib produced a synergistic effect in decreasing cell viability in an in vitro hepatocellular carcinoma (HCC) model. -siRNA NPs together with sorafenib or sunitinib greatly inhibited cell proliferation, showing only 39.29 ± 2.72 and 44.04 ± 3.05% cell viability, respectively. Moreover, quantitative reverse transcription PCR (qRT-PCR) demonstrated that -siRNA incorporated with NPs could significantly silence -mRNA expression compared to unloaded NPs. Interestingly, the expression level of -mRNA was further decreased to 28.53 ± 5.10% when sunitinib was added. Therefore, this finding was considered a new promising candidate for HCC treatment in reducing cell proliferation and enhancing therapeutic outcomes.
血管生成抑制剂药物已被探索作为癌症治疗的重要药理学药物，包括肝细胞癌。这些药物有几个缺点，如耐药性、非特异性毒性和全身副作用。因此，药物和小干扰 RNA 的联合治疗可能是一种很有前途的选择，可以实现高治疗效果，同时允许较低的全身剂量。因此，我们研究了在聚合纳米颗粒（NPs）上添加载有甲胎蛋白 siRNA（-siRNA）的药物。载有 -siRNA 的 NPs 成功地在平均尺寸为 242.00 ± 2.54 nm 的情况下合成。-siRNA NPs 与低剂量舒尼替尼联合治疗在体外肝癌（HCC）模型中降低细胞活力方面产生协同作用。-siRNA NPs 与索拉非尼或舒尼替尼一起极大地抑制了细胞增殖，分别显示出仅 39.29 ± 2.72%和 44.04 ± 3.05%的细胞活力。此外，定量逆转录 PCR（qRT-PCR）表明，与未加载的 NPs 相比，载有 NPs 的 -siRNA 可以显著沉默 -mRNA 的表达。有趣的是，当加入舒尼替尼时，-mRNA 的表达水平进一步降低至 28.53 ± 5.10%。因此，这一发现被认为是降低细胞增殖和提高治疗效果的 HCC 治疗的一个新的有前途的候选药物。
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