Combined Inhibition of SREBP and m-TORC1 Signaling Synergistically Inhibits the Proliferation of B Cell Lymphoma

Sterol regulatory element-binding protein (SREBP) signaling plays a crucial role in maintaining sterol homeostasis during B cell activation and the proliferation of germinal center B cells. It is unclear whether this pathway can be targeted to effectively treat B cell lymphoma. We discovered that inhibiting SREBP signaling or its downstream target HMG-CoA reductase (HMGCR) using Fatostatin or Simvastatin effectively restrains the proliferation of B cell lymphoma cells. However, B cell lymphoma cells activate the mTORC1-pS6 pathway in response to statin treatment, suggesting a possible mechanism to counteract statin-induced cell cycle arrest. Combining low dose statin treatment with the mTORC1 inhibitor rapamycin demonstrates a synergistic effect in inhibiting B cell lymphoma proliferation, cell cycle progression and lipid raft generation. These findings emphasize the potential of a combined therapy approach targeting both SREBP and mTORC1 as a novel treatment strategy for B cell lymphoma.

Author dc:creator

• Zhu, Zhenhan

Advisor dc:contributor.advisor

• Luo, Wei

• Statins
• SREBP
• mTORC1
• B cell lymphoma

Language dc:language.iso

en_US

Identifier URI

https://doi.org/10.7912/5FFC-S592

OAI identifier oai:identifier

oai:scholarworks.indianapolis.iu.edu:1805/42652