Imatinib inhibits oral squamous cell carcinoma by suppressing the PI3K/AKT/mTOR signaling pathway

Ma, Lei; Huang, Ke; Zhang, Haibo; Kim, Eungyung; Kim, Hyeonjin; Liu, Zhibin; Kim, Chae Yeon; Park, Kanghyun; Raza, Muhammad Atif; Kim, Kirim; Yi, Junkoo; Sung, Yonghun; Ryoo, Zae Young; Kim, Yong-Gun; Kim, Myoung Ok

doi:10.7150/jca.88555

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J Cancer 2024; 15(3):659-670. doi:10.7150/jca.88555 This issue Cite

Research Paper

Imatinib inhibits oral squamous cell carcinoma by suppressing the PI3K/AKT/mTOR signaling pathway

Lei Ma^1,†, Ke Huang^1,†, Haibo Zhang², Eungyung Kim¹, Hyeonjin Kim¹, Zhibin Liu¹, Chae Yeon Kim¹, Kanghyun Park¹, Muhammad Atif Raza¹, Kirim Kim³, Junkoo Yi⁴, Yonghun Sung⁵, Zae Young Ryoo⁶, Yong-Gun Kim⁷, Myoung Ok Kim^1,✉

1. Department of Animal Science and Biotechnology, Research Center for Horse Industry, Kyungpook National University, Sangju, Gyeongsangbuk-do 37224, Republic of Korea.
2. College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, China.
3. Department of Dental Hygiene, Kyungpook National University, Sangju, Republic of Korea.
4. School of Animal Life Convergence Science, Hankyong National University, Anseong, 17579, Republic of Korea.
5. Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu 41061, Republic of Korea.
6. School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea
7. Department of Periodontology, Kyungpook National University School of Dentistry, Daegu, South Korea.
^† Equal contribution.

Citation:

Ma L, Huang K, Zhang H, Kim E, Kim H, Liu Z, Kim CY, Park K, Raza MA, Kim K, Yi J, Sung Y, Ryoo ZY, Kim YG, Kim MO. Imatinib inhibits oral squamous cell carcinoma by suppressing the PI3K/AKT/mTOR signaling pathway. J Cancer 2024; 15(3):659-670. doi:10.7150/jca.88555. https://www.jcancer.org/v15p0659.htm

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Abstract

Oral squamous cell carcinoma (OSCC) is a prevalent oral and maxillofacial cancer with high mortality as OSCC cells readily invade tissues and metastasize to cervical lymph nodes. Although imatinib exhibits potential anticancer and remarkable clinical activities that therapeutically affect several cancer types, its specific impact on OSCC has yet to be fully explored. Therefore, this study investigated the potential anticancer effect of imatinib on OSCC cells and the underlying mechanisms. The Cell Counting Kit-8 was used to determine the impact of imatinib on cell viability. Then, morphological cell proliferation analysis was conducted to examine how imatinib impacted OSCC cell growth. Moreover, OSCC cell migration was determined through wound-healing assays, and colony formation abilities were investigated through the soft agar assay. Lastly, the effect of imatinib on OSCC cell apoptosis was verified with flow cytometry, and its inhibitory mechanism was confirmed through Western blot. Our results demonstrate that imatinib effectively inhibited OSCC cell proliferation and significantly curtailed OSCC cell viability in a time- and concentration-dependent manner. Furthermore, imatinib suppressed migration and colony formation while promoting OSCC cell apoptosis by enhancing p53, Bax, and PARP expression levels and reducing Bcl-2 expression. Imatinib also inhibited the PI3K/AKT/mTOR signaling pathway and induced OSCC cell apoptosis, demonstrating the potential of imatinib as a treatment for oral cancer.

Keywords: imatinib, oral squamous cell carcinoma, proliferation, viability, PI3K/AKT/mTOR signaling pathway

Citation styles

APA

Ma, L., Huang, K., Zhang, H., Kim, E., Kim, H., Liu, Z., Kim, C.Y., Park, K., Raza, M.A., Kim, K., Yi, J., Sung, Y., Ryoo, Z.Y., Kim, Y.G., Kim, M.O. (2024). Imatinib inhibits oral squamous cell carcinoma by suppressing the PI3K/AKT/mTOR signaling pathway. Journal of Cancer, 15(3), 659-670. https://doi.org/10.7150/jca.88555.

ACS

Ma, L.; Huang, K.; Zhang, H.; Kim, E.; Kim, H.; Liu, Z.; Kim, C.Y.; Park, K.; Raza, M.A.; Kim, K.; Yi, J.; Sung, Y.; Ryoo, Z.Y.; Kim, Y.G.; Kim, M.O. Imatinib inhibits oral squamous cell carcinoma by suppressing the PI3K/AKT/mTOR signaling pathway. J. Cancer 2024, 15 (3), 659-670. DOI: 10.7150/jca.88555.

NLM

CSE

Ma L, Huang K, Zhang H, Kim E, Kim H, Liu Z, Kim CY, Park K, Raza MA, Kim K, Yi J, Sung Y, Ryoo ZY, Kim YG, Kim MO. 2024. Imatinib inhibits oral squamous cell carcinoma by suppressing the PI3K/AKT/mTOR signaling pathway. J Cancer. 15(3):659-670.

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