Int J Biol Sci 2022; 18(2):473-490. doi:10.7150/ijbs.65824 This issue

Research Paper

ID09, A Newly-Designed Tubulin Inhibitor, Regulating the Proliferation, Migration, EMT Process and Apoptosis of Oral Squamous Cell Carcinoma

Qiushi Feng1,2*, Panpan Yang1,2*, He Wang1,2, Congshan Li1,2, Tomoka Hasegawa4, Zhaopeng Liu2,3*, Minqi Li1,2✉

1. Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, 250012, China
2. Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China
3. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, P. R. China
4. Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8586, Japan
* Qiushi Feng and Panpan Yang contributed equally to this work

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Citation:
Feng Q, Yang P, Wang H, Li C, Hasegawa T, Liu Z, Li M. ID09, A Newly-Designed Tubulin Inhibitor, Regulating the Proliferation, Migration, EMT Process and Apoptosis of Oral Squamous Cell Carcinoma. Int J Biol Sci 2022; 18(2):473-490. doi:10.7150/ijbs.65824. Available from https://www.ijbs.com/v18p0473.htm

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Abstract

Graphic abstract

Microtubules, a major target in oral squamous cell carcinoma (OSCC) chemotherapy, contribute to multiple malignant biological behaviors, including proliferation, migration, and epithelial-mesenchymal transition (EMT). Surpassing traditional tubulin inhibitors, ID09 emerges with brilliant solubility, photostability, and drug-sensitivity in multidrug-resistant cells. Its anti-tumor effects have been briefly verified in lung adenocarcinoma and hepatocellular carcinoma. However, whether OSCC is sensitive to ID09 and the potential mechanisms remain ambiguous, which are research purposes this study aimed to achieve. Various approaches were applied, including clone formation assay, flow cytometry, wound healing assay, Transwell assay, cell counting kit-8 assay, Western blot, qRT-PCR, and in vivo experiment. The experimental results revealed that ID09 not only contributed to cell cycle arrest, reduced migration, and reversed EMT, but accelerated mitochondria-initiated apoptosis. Remarkably, Western blot detected diminishment in expression of Mcl-1 due to the deactivation of Ras-Erk pathway, resulting in ID09-induced apoptosis, proliferation and migration suppression, which could be offset by Erk1/2 phosphorylation agonist Ro 67-7476. This study initially explored the essential role Mcl-1 played and the regulatory effect of Ras-Erk pathway in anti-cancer process triggered by tubulin inhibitor, broadening clinical horizon of tubulin inhibitors in oral squamous cell carcinoma chemotherapy application.

Keywords: Tubulin Inhibitor ID09, Malignant Biological Behaviors, Apoptosis, Oral Squamous Cell Carcinoma, Mcl-1, Ras-Erk Pathway