Anlotinib Inhibiting Mantle Cell Lymphoma Proliferation and Inducing Apoptosis through PI3K/AKT/mTOR Pathway
- PMID: 38659267
- DOI: 10.2174/0115665240284638240408081133
Anlotinib Inhibiting Mantle Cell Lymphoma Proliferation and Inducing Apoptosis through PI3K/AKT/mTOR Pathway
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; mammalian target of rapamycin; mantle cell lymphoma; phosphoinositide 3-kinase; tumour microenvironment.
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- LGF21H080002/Zhejiang Provincial Natural Science Foundation of China
- 2022KY1113/Medical Health Science and Technology Project of Zhejiang Provincial Health Commission
- 2022ZB324/Traditional Chinese Medicine Administration of Zhejiang Province
- 2021KY273/Zhejiang Medical and Health Science and Technology Project
- 2022S032/Ningbo Public Welfare Fund Project
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