10.6084/M9.FIGSHARE.16999096
Shaojuan Song
Shaojuan
Song
Xin Xia
Xin
Xia
Jiajia Qi
Jiajia
Qi
Xiaopei Hu
Xiaopei
Hu
Qian Chen
Qian
Chen
Jiang Liu
Jiang
Liu
Ning Ji
Ning
Ji
Hang Zhao
Hang
Zhao
Silmitasertib-induced macropinocytosis promoting DDP intracellular uptake to enhance cell apoptosis in oral squamous cell carcinoma
<p>Cisplatin (DDP) is a first-line chemotherapeutic drug applied for the treatment of oral squamous cell carcinoma (OSCC). The anticancer activity of DDP is tightly linked to its intracellular uptake. It is unwise to increase the DDP intake by increasing the dose or shortening the dosing interval because of the severe systemic toxicity (nephrotoxicity, ototoxicity and neurotoxicity) in DDP application. The main uptake pathways of DDP include passive diffusion and active transporter transport. Therefore, finding additional uptake pathways that can improve the effective intracellular concentration of DDP is critical. Macropinocytosis, an endocytic mechanism for extracellular material absorption, contributes to the intracellular uptake of anticancer drugs. No research has been conducted to determine whether macropinocytosis can augment the intracellular uptake of DDP in OSCC cells or not. Based on that, we proved for the first time that silmitasertib (previously CX-4945) could trigger macropinocytosis, which may increase the intracellular uptake of DDP and enhance apoptosis via <i>in vivo</i> and <i>in vitro</i> experiments. We hope that our findings will inspire a new approach for the application of DDP in cancer treatment.</p>
Biophysics
Cell Biology
Pharmacology
Biotechnology
Chemical Sciences not elsewhere classified
Immunology
Cancer
Hematology
Infectious Diseases
Computational Biology
Taylor & Francis
2021
2021-11-12
2024-03-21
Journal contribution
1587628 Bytes
10.1080/10717544.2021.2000677
CC BY 4.0