Department of Obstetrics and Gynecology, The Women and Children Hospital Affiliated to Jiaxing University, 2468 Middle Ring Eastern Road, Jiaxing City, Zhejiang 314000, China.
Department of Obstetrics and Gynecology, The Women and Children Hospital Affiliated to Jiaxing University, 2468 Middle Ring Eastern Road, Jiaxing City, Zhejiang 314000, China.
Biomed Pharmacother. 2018 Nov;107:849-859. doi: 10.1016/j.biopha.2018.08.042. Epub 2018 Aug 22.
Choriocarcinoma is a highly aggressive and vascular cancer. The main treatment for choriocarcinoma is the chemotherapy associated with severe side effects. Therefore, the development of novel strategies to eliminate choriocarcinoma is crucial for increasing the health of women. SATB1 (special AT-rich sequence binding protein 1) participates in tissue-specific gene expression and higher-order chromatin organization, and could promote cancer progression and invasion. For the first time, we hereby demonstrated that the expression of SATB1 was increased by 19 folds in choriocarcinoma cells compared with the normal chorionic cell line, and inhibition of SATB1 expression could markedly inhibit the proliferation of choriocarcinoma cells. Then we developed the gene drug delivery system EGFR-LPDS (epidermal growth factor receptor aptamer-conjugated liposome-polycation-DNA complex loaded with SATB1 siRNA) to increase the delivery and therapeutic effect of SATB1 siRNA against choriocarcinoma cells. The results showed that EGFR-LPDS could specifically target choriocarcinoma cells, resulting in significant inhibition of SATB1 expression, growth inhibitory effect and apoptosis in EGFR over-expressing choriocarcinoma cells in vitro. Notably, EGFR-LPDS could inhibit the expression of SATB1 in choriocarcinoma xenograft in mice, and exhibited the best therapeutic efficacy against mice bearing choriocarcinoma xenograft compared with other controls. Notably, EGFR-LPDS achieved a striking tumor weight inhibitory rate of 81.4%. This is the first report of the therapeutic efficacy of SATB1 siRNA towards choriocarcinoma, and the increased SATB1 siRNA delivery by nanoparticles to choriocarcinoma cells using EGFR aptamers. Thus, EGFR-LPDS represents an up-and coming approach for choriocarcinoma therapy. Considering that there are still limited treatment strategies for choriocarcinoma therapy, patients with choriocarcinoma may be beneficial from this gene therapy.
绒癌是一种高度侵袭性和血管丰富的癌症。绒癌的主要治疗方法是化疗，但化疗会伴随严重的副作用。因此，开发新型策略以消除绒癌对于提高女性健康至关重要。SATB1（特异性富含 AT 的序列结合蛋白 1）参与组织特异性基因表达和高级染色质组织，能够促进癌症的进展和侵袭。我们首次证明，与正常绒毛膜细胞系相比，绒癌细胞中 SATB1 的表达增加了 19 倍，抑制 SATB1 的表达可以显著抑制绒癌细胞的增殖。然后，我们开发了基因药物传递系统 EGFR-LPDS（表皮生长因子受体适体偶联脂质体-聚阳离子-DNA 复合物负载 SATB1 siRNA），以增加 SATB1 siRNA 对绒癌细胞的传递和治疗效果。结果表明，EGFR-LPDS 可以特异性靶向绒癌细胞，导致 SATB1 表达显著抑制、EGFR 过表达绒癌细胞的生长抑制作用和凋亡作用。值得注意的是，EGFR-LPDS 可以抑制小鼠绒癌异种移植中的 SATB1 表达，并表现出比其他对照组更好的治疗效果。值得注意的是，EGFR-LPDS 对肿瘤重量的抑制率达到了 81.4%。这是首次报道 SATB1 siRNA 对绒癌的治疗效果，以及使用 EGFR 适体将纳米颗粒递送到绒癌细胞中的 SATB1 siRNA 表达增加。因此，EGFR-LPDS 代表了绒癌治疗的一种新方法。鉴于绒癌治疗的策略仍然有限，绒癌患者可能会从这种基因治疗中受益。
