Research Paper Volume 15, Issue 21 pp 12225—12250
Plumbagin has an inhibitory effect on the growth of TSCC PDX model and it enhances the anticancer efficacy of cisplatin
- 1 Department of Stomatology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
- 2 Medical College, Nanchang University, Nanchang, Jiangxi 330006, China
Received: June 6, 2023 Accepted: October 2, 2023 Published: November 3, 2023
https://doi.org/10.18632/aging.205175How to Cite
Copyright: © 2023 Xin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Head and neck squamous cell carcinomas are the sixth most common malignant tumors worldwide. Tongue squamous cell carcinoma is a common malignant tumor of this type, and it is associated with poor prognosis, a high rate of recurrence and a low survival rate. Plumbagin is derived from Plumbago zeylanica L, several studies report that plumbagin could inhibit cell, tumor metastasis, induce apoptosis in various cancer cells. Patient-derived xenograft (PDX) model can maintain the heterogeneity and microenvironment of human tumors, is a powerful research tool for developing potentially effective therapies for TSCC.
Methods: Tumor tissues obtained from TSCC patients were implanted into immunodeficient mice to establish TSCC PDX models. Subsequently, the PDX models were used to evaluate the anti-tumor effects of plumbagin on TSCC. Furthermore, we conducted next-generation sequencing (NGS) and explored the mRNA expression profiles between the treatment and control groups. We selected eight mRNAs related to the characteristics and prognosis of TSCC patients for further analysis.
Results: Plumbagin could inhibit the growth of TSCC PDX models and inhibit expression of Akt/mTOR pathway. In addition, plumbagin was shown to increase drug sensitivity to cisplatin. The eight mRNAs selected for further analysis, AXL, SCG5, VOPP1, DCBLD2 and DRAM1 are cancer-promoting genes, DUSP1, AQP5 and BLNK are cancer suppressor genes. And they were related to the diagnosis, growth, prognosis, and immune cell infiltration in TSCC patients.
Conclusion: Plumbagin exhibits an inhibitory effect on the growth of the PDX model of TSCC. Moreover, plumbagin enhances the inhibitory effects of cisplatin.
Abbreviations
HNSCC: Head and neck squamous cell carcinoma; TSCC: Tongue squamous cell carcinoma; PDX: Patient-derived xenograft; NGS: Next-generation sequencing; TCM: Traditional Chinese medicine; HE: Hematoxylin-Eosin; IHC: Immunohistochemistry; PCR: Polymerase Chain Reaction; RT-qPCR: Reverse Transcription-Quantitative Polymerase Chain Reaction; ROC: Receiver operating characteristic; AUC: Area under the curve; AXL: Anexelekto; RTKs: Receptor tyrosine kinases; SCG5: Secretogranin V; VOPP1: Prosurvival Protein 1; ECs: Endothelial cells; DRAM1: DNA damage-regulated autophagy modulator 1; MAPK: Mitogen-activated protein kinase; DUSPs: Dual-specificity phosphatases; AQP5: Aquaporin 5; BLNK: B-cell linker protein.