Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, People's Republic of China.
Drug Des Devel Ther. 2021 Jan 13;15:171-183. doi: 10.2147/DDDT.S282777. eCollection 2021.
Sodium cantharidinate (SC) has been broadly applied in lung cancer treatment in China, while its specific function in cervical cancer (CC), a great contributor to death of female reproductive system cancers, remains unclear. Our research evaluated the anti-tumor effects of SC in CC and the mechanism involved.
First, cisplatin (DDP)-resistant Caski-1 and ME180 cell lines were developed and treated with SC. The effects of SC on CC cell growth were then evaluated. Subsequently, the genes targeted by SC were predicted via the bioinformatics website. The correlations between PTPN1 expression and tumor stage, lymph node metastasis and tumor differentiation were examined. We further conducted rescue experiments by overexpressing PTPN1 in CC cells, followed by SC and cisplatin treatments. The activation of the PI3K/AKT pathway in CC cells, and the effect of SC on the growth and drug resistance of Caski-1 cells in vivo were investigated.
The sensitivity of Caski-1 and ME180 cells to DDP was increased after SC treatment, which also enhanced the inhibitory effect of DDP on the cell growth. By prediction, we found that SC could target PTPN1. Patients with high expression of PTPN1 had higher clinical stage, lymph node metastasis and lower tumor differentiation. SC inhibited PTPN1 expression. Overexpression of PTPN1 attenuated the effect of SC. Furthermore, PTPN1 activated the PI3K/AKT pathway. Moreover, SC treatment inhibited the growth and drug resistance of Caski-1 cells in vivo.
SC promotes drug sensitivity of CC cells to DDP by targeting PTPN1, thereby impairing the PI3K/AKT pathway.
在中国，临床上已经广泛应用苦参素（SC）治疗肺癌，但苦参素在宫颈癌（CC）中的具体作用，即女性生殖系统癌症死亡的主要原因之一，仍不清楚。我们的研究评估了苦参素在宫颈癌中的抗肿瘤作用及其相关机制。
首先，建立顺铂（DDP）耐药的 Caski-1 和 ME180 细胞系，并给予苦参素处理，然后评估苦参素对 CC 细胞生长的影响。接着，通过生物信息学网站预测苦参素作用的靶基因。检测 PTPN1 表达与肿瘤分期、淋巴结转移和肿瘤分化的相关性。进一步通过在 CC 细胞中转染 PTPN1 过表达质粒进行挽救实验，然后给予苦参素和顺铂处理。研究苦参素对 CC 细胞中 PI3K/AKT 通路的激活作用，以及苦参素对体内 Caski-1 细胞生长和耐药性的影响。
苦参素处理后，Caski-1 和 ME180 细胞对 DDP 的敏感性增加，且 DDP 对细胞生长的抑制作用增强。通过预测，我们发现苦参素可以作用于 PTPN1。PTPN1 高表达的患者具有更高的临床分期、淋巴结转移和更低的肿瘤分化。苦参素抑制 PTPN1 的表达。过表达 PTPN1 减弱了苦参素的作用。此外，PTPN1 激活了 PI3K/AKT 通路。此外，苦参素处理抑制了体内 Caski-1 细胞的生长和耐药性。
苦参素通过靶向 PTPN1 促进 CC 细胞对 DDP 的敏感性，从而抑制 PI3K/AKT 通路。
