Lenvatinib Suppresses Protein Kinase B Signaling and Induces Apoptosis in Osteosarcoma Cells

Chun-Yi Li; Hsin-Chuan Chen; Chih-Ying Liao; Fei-Ting Hsu; Kuang-Chen Hung; Kuo-Ching Liu; Jaw-Chyun Chen; Ming-Chou Ku

doi:10.21873/anticanres.16790

Lenvatinib Suppresses Protein Kinase B Signaling and Induces Apoptosis in Osteosarcoma Cells

Anticancer Res. 2024 Jan;44(1):85-92. doi: 10.21873/anticanres.16790.

Authors

Chun-Yi Li^#¹, Hsin-Chuan Chen^#^{1

2}, Chih-Ying Liao^#³, Fei-Ting Hsu⁴, Kuang-Chen Hung^{5

6

7

8

9}, Kuo-Ching Liu¹⁰, Jaw-Chyun Chen¹¹, Ming-Chou Ku^{12

13}

Affiliations

¹ Department of Orthopedics, Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.
² Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C.
³ Department of Radiation Oncology, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.
⁴ Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C.
⁵ Department of Surgery, Zuoying Armed Forces General Hospital, Kaohsiung, Taiwan, R.O.C.
⁶ Department of Surgery, National Defense Medical Center, Taipei, Taiwan, R.O.C.
⁷ Department of Surgery, Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C.
⁸ Central Taiwan University of Science and Technology, Taichung, Taiwan, R.O.C.
⁹ National Chin-Yi University of Technology, Taichung, Taiwan, R.O.C.
¹⁰ Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan, R.O.C.
¹¹ Department of Medicinal Botanicals and Foods on Health Applications, Da-Yeh University, Changhua, Taiwan, R.O.C.
¹² Department of Orthopedics, Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.; showjoeku@gmail.com.
¹³ Department of Medical Imaging and Radiologic Sciences, Central Taiwan University of Science and Technology, Taichung, Taiwan, R.O.C.

^# Contributed equally.

PMID: 38160012
DOI: 10.21873/anticanres.16790

Abstract

Background/aim: Lenvatinib, an oral multikinase inhibitor, has demonstrated promising activity in patients with osteosarcoma (OS). Therefore, it is worth exploring the inhibitory efficacy and mechanism of action of lenvatinib in osteosarcoma. The primary goal of this study was to examine the inhibitory effectiveness and mechanism of lenvatinib on the growth and invasion of OS cells.

Materials and methods: The effects of lenvatinib on cell viability, apoptosis, protein kinase B (AKT) activation, its downstream effector proteins involved in tumor progression, and invasion capability were assessed using MTT assay, flow cytometry, western blotting, and invasion/migration assay on U-2 OS and MG63 cells.

Results: Lenvatinib effectively induced cytotoxicity, apoptosis, as well as extrinsic and intrinsic apoptotic signaling in OS cells. Lenvatinib also significantly decreased the invasion/migration capability, AKT activation, and downstream effector proteins.

Conclusion: The anti-OS effect of lenvatinib may be associated with the induction of apoptosis and the inactivation of AKT.

Keywords: AKT; Lenvatinib; apoptosis; invasion; osteosarcoma.

MeSH terms

Apoptosis
Bone Neoplasms* / pathology
Cell Line, Tumor
Cell Movement
Cell Proliferation
Humans
Osteosarcoma* / pathology
Proto-Oncogene Proteins c-akt / metabolism

Substances

Proto-Oncogene Proteins c-akt
lenvatinib