Anlotinib Inhibiting Mantle Cell Lymphoma Proliferation and Inducing Apoptosis through PI3K/AKT/mTOR Pathway

Jiaping Wang; Zhijuan Xu; Yanli Lai; Yanli Zhang; Ping Zhang; Qitian Mu; Shujun Yang; Lixia Sheng; Guifang Ouyang

doi:10.2174/0115665240284638240408081133

Anlotinib Inhibiting Mantle Cell Lymphoma Proliferation and Inducing Apoptosis through PI3K/AKT/mTOR Pathway

Curr Mol Med. 2024 Apr 24. doi: 10.2174/0115665240284638240408081133. Online ahead of print.

Authors

Jiaping Wang¹, Zhijuan Xu¹, Yanli Lai¹, Yanli Zhang¹, Ping Zhang¹, Qitian Mu¹, Shujun Yang¹, Lixia Sheng¹, Guifang Ouyang¹

Affiliation

¹ Ningbo Clinical Research Center for Hematological Malignancies, Department of hematology, the First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315000, China.

PMID: 38659267
DOI: 10.2174/0115665240284638240408081133

Abstract

Background: This study investigates the inhibitory mechanism of anlotinib on human Mantle Cell Lymphoma (MCL) cells through in vitro and in vivo experiments.

Methods: In vitro cellular experiments validate the effects of anlotinib on MCL cell proliferation and apoptosis. Moreover, a subcutaneous xenograft nude mice model of Mino MCL cells was established to assess the anti-tumour effect and tumour microenvironment regulation of anlotinib in vivo.

Results: The results indicate that MCL cell proliferation was significantly inhibited upon anlotinib exposure. The alterations in the expression of apoptosis-related proteins further confirm that anlotinib can induce apoptosis in MCL cells. Additionally, anlotinib significantly reduced the PI3K/Akt/mTOR phosphorylation level in MCL cells. The administration of a PI3K phosphorylation agonist, 740YP, could reverse the inhibitory effect of anlotinib on MCL. In the xenograft mouse model using Mino MCL cells, anlotinib treatment led to a gradual reduction in body weight and a significant increase in survival time compared to the control group. Additionally, anlotinib attenuated PD-1 expression and elevated inflammatory factors, CD4, and CD8 levels in tumour tissues.

Conclusion: Anlotinib effectively inhibits proliferation and induces apoptosis in MCL both in vitro and in vivo. This inhibition is likely linked to suppressing phosphorylation in the PI3K/Akt/mTOR pathway.

Keywords: AKT; anlotinib; apoptosis; chronic myeloid mantle cell lymphoma; mammalian target of rapamycin (mTOR); phosphoinositide 3-kinase; protein kinase B.