Browsing by Author "Zhu, Zhenhan"

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    Combined Inhibition of SREBP and m-TORC1 Signaling Synergistically Inhibits the Proliferation of B Cell Lymphoma
    (2024-06) Zhu, Zhenhan; Luo, Wei; Capitano, Meagan L; Yuan, Xue
    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.
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    The Combined Inhibition of SREBP and mTORC1 Signaling Synergistically Inhibits B‐Cell Lymphoma
    (Wiley, 2024) Zhu, Zhenhan; Jiang, Wenxia; Zhou, Jiehao; Maldeney, Alexander Robert; Liang, Jingru; Yang, Jing; Luo, Wei; Microbiology and Immunology, School of Medicine
    Background: The sterol regulatory element-binding protein (SREBP) pathway is essential for maintaining sterol homeostasis during B cell activation and germinal center B cell proliferation. However, its potential as a therapeutic target to treat B-cell lymphoma remains unclear. Methods: We examined SREBP protein expression in human B-cell lymphoma samples using immunohistochemistry. Additionally, we conducted in vitro studies using SREBP signaling inhibitors in combination with rapamycin to assess their effects on cell proliferation and lipid metabolism in B-cell lymphoma cells. Results: Our analysis revealed high levels of SREBP2 protein expression in human B-cell lymphoma samples. Inhibiting SREBP signaling or its downstream target HMG-CoA reductase (HMGCR) with Fatostatin or Simvastatin effectively suppressed B-cell lymphoma cell proliferation. However, B-cell lymphoma cells responded to statin treatment by activating the mTORC1-pS6 pathway, suggesting a compensatory mechanism to overcome statin-induced cell cycle arrest. Combining low-dose statin treatment with the mTOR inhibitor rapamycin produced a synergistic effect, significantly inhibiting B-cell lymphoma proliferation, cell cycle progression, and lipid raft formation. Conclusions: These results highlight the potential of a combined therapeutic approach targeting both SREBP and mTORC1 as a novel strategy for treating B-cell lymphoma.