Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei, 430060, P. R. China.
Department of Anesthesiology, Renmin Hospital of Wuhan University, No. 238, Jie-Fang Road, Wuhan, Hubei, 430060, P. R. China.
J Transl Med. 2024 Nov 19;22(1):1043. doi: 10.1186/s12967-024-05855-8.
The novel nanomaterials PNA-TN (PN) and PNA-TN-Dox (PND) have been shown to have strong inhibitory effects on breast cancer; however, it is unclear whether PN and PND have anti-head and neck squamous cell carcinoma (HNSCC) activity, and their potential mechanisms of activity are unknown. So, our study aims to explore the therapeutic effects of PN and PND on HNSCC and their possible mechanisms.
We used a series of phenotypic research to evaluate the effects of PN + Laser (L) and PND + L on the biological function of HNSCC cells in vitro and in vivo. We subsequently used mechanism research to examine changes in mRNA and protein expression related to apoptosis, epithelial‒mesenchymal transition (EMT), and the JNK signalling pathway.
Our study revealed that PN and PND have strong inhibitory effects on HNSCC cells both in vitro and in vivo. In vitro, PN and PND significantly inhibited the proliferation, migration, invasion and EMT ability of HNSCC cells and promoted apoptosis; the inhibitory effect in the PND + L group was significantly greater than that in the PN + L group. In vivo, both treatments led to significant reductions in tumour volume and weight. Notably, the tumour volume and weight in the PND + L group were significantly lower than those in the PN + L group. Mechanism research confirmed that PN + L activated the expression of apoptosis-related proteins and inhibited the expression of EMT-related proteins via the JNK pathway. Furthermore, the anti-HNSCC effect of PN + L was blocked after the use of a JNK pathway inhibitor.
Treatment with PN + L or PND + L significantly inhibited the malignant progress of HNSCC cells, and the therapeutic effect of PND + L was significantly stronger than that of PN + L. The JNK signalling pathway is a key mechanism by which PN exerts its anti-HNSCC activity.
新型纳米材料 PNA-TN(PN)和 PNA-TN-阿霉素(PND)已被证明对乳腺癌具有很强的抑制作用;然而,PN 和 PND 是否具有抗头颈部鳞状细胞癌(HNSCC)的活性尚不清楚,其潜在的作用机制也不清楚。因此,本研究旨在探讨 PN 和 PND 对 HNSCC 的治疗作用及其可能的机制。
我们使用一系列表型研究来评估 PN+激光(L)和 PND+L 对体外和体内 HNSCC 细胞生物学功能的影响。随后,我们使用机制研究来检测与细胞凋亡、上皮-间充质转化(EMT)和 JNK 信号通路相关的 mRNA 和蛋白表达的变化。
我们的研究表明,PN 和 PND 对体外和体内的 HNSCC 细胞均具有很强的抑制作用。在体外,PN 和 PND 显著抑制 HNSCC 细胞的增殖、迁移、侵袭和 EMT 能力,并促进细胞凋亡;PND+L 组的抑制作用明显大于 PN+L 组。在体内,两种治疗均导致肿瘤体积和重量的显著减少。值得注意的是,PND+L 组的肿瘤体积和重量明显低于 PN+L 组。机制研究证实,PN+L 通过 JNK 通路激活凋亡相关蛋白的表达,抑制 EMT 相关蛋白的表达。此外,使用 JNK 通路抑制剂后,PN+L 的抗 HNSCC 作用被阻断。
PN+L 或 PND+L 治疗显著抑制 HNSCC 细胞的恶性进展,PND+L 的治疗效果明显强于 PN+L。JNK 信号通路是 PN 发挥抗 HNSCC 活性的关键机制。