Drug Repurposing Flubendazole to Suppress Tumorigenicity via PCSK9-dependent Inhibition and Potentiate Lenvatinib Therapy for Hepatocellular Carcinoma

Jin, Wenjiao; Yu, Jin Hai; Shao‐Horn, Yang; Lin, Hechun; Liu, Tengfei; Chen, Jing; Chen, Ge; Zhao, Fangyu; Geng, Qingshan; Lin, Min; Jiang, Shuqing; Cui, Ying; Chen, Taoyang; Jiang, Guoping; Li, Jinjun; Miao, Chunxiao; Xiao, Xiuying; Li, Hong

doi:10.7150/ijbs.81415

Cited by 10 publications

(1 citation statement)

References 69 publications

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“…Flubendazole interfered with the polymerization of microtubules by binding to the inner surface of α/β microtubule protein heterodimers, thus affecting normal physiological functions such as mitosis, intracellular material transport, cell motility and cell morphology maintenance 12 . A growing number of studies have shown that Flubendazole play a role in affecting the viability and invasion of tumor cell, including breast cancer, melanoma, prostate cancer, liver cancer and colon cancer [13][14][15][16][17] . However, few studies were performed to investigate its role in PDAC.…”

Section: Introductionmentioning

confidence: 99%

Flubendazole presents anti-tumor effects by promoting cell cycle arrest and inhibiting the invadopodia in pancreatic cancer

Zhao,

Wang,

Huang

et al. 2024

Preprint

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Pancreatic ductal adenocarcinoma (PDAC) is characterised by its high aggressive biological tumor behavior leading to a poor prognosis. The existing chemotherapy regimes have considerable limitations such as drug resistance and serious adverse effects. Flubendazole is an antihelmintic drug with highly safety that is recently reported to be a potential anti-tumor agent in various types of human cancer cells. We conducted a series of assays to explore its role in PDAC, like CCK8 assays, transwell-migration and invasion assays. In addition, we constructed the invadopodia model in vitro to investigate the effect of flubendazole on invadopodia. We found that flubendazole could inhibit the viability of PDAC cells dose-dependently and time-dependently. It also caused G2/M arrest by disrupting the microtubule and also induce apoptosis. The migration of PDAC cells was attenuated and could be partly explained by the disruption of EMT caused by flubendazole. Besides, the invasion was weakened by flubendazole and the number of cells with mature invadopodia was also decreased. Moreover, it interfered the formation and maturation of invadopodia by inhibiting PI3K/Akt pathway and Src-mediated Tks5 phosphorylation, and thus inhibit the metastasis of PDAC cells. Due to its high safety, it may provide a novel insight for the prevention and treatment of pancreatic cancer metastasis.

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Section: Introductionmentioning

confidence: 99%

Flubendazole presents anti-tumor effects by promoting cell cycle arrest and inhibiting the invadopodia in pancreatic cancer

Zhao,

Wang,

Huang

et al. 2024

Preprint

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Fluorinated Chitosan‐Mediated Transepithelial Delivery of Intravesical Dual‐Drug Immunotherapeutic for Bladder Cancer Therapy

Feng,

Huang,

Lei

et al. 2024

Advanced Therapeutics

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Intravesical instillation‐based immunotherapy for bladder‐preservation of bladder cancer (BCa) treatment has not been explored. In the current study, two irrigated nano‐formulations of immunological adjuvant‐fluorinated chitosan (FCS) and therapeutic antibody‐FCS are developed for synergistic immunotherapy against BCa. In this system, FCS is employed as a transepithelial carrier to assemble with bovine serum albumin (BSA)‐flubendazole (FBZ) complex and anti‐PD‐1 (αPD‐1) respectively, to facilitate efficient transepithelial delivery of intravesical FBZ‐BSA and αPD‐1 though transiently regulating the distribution of tight junction proteins on bladder epithelium. In addition, the FBZ–BSA complex exhibits tumor microenvironment‐responsive charge reversal and BSA carrier‐broken effects to drive tumor‐targeted dissociation and drug release of FBZ–BSA/FCS. Moreover, FBZ not only promotes apoptosis and inhibits glycolysis in cancer cells but also displays adjuvant properties to activate potent immune responses through IL‐12/IFN‐γ pathway. Interestingly, combined perfusion of FBZ–BSA/FCS and αPD‐1/FCS nano‐formulations can significantly activate the tumor immune microenvironment, especially CD8+ T cell infiltration and αPD‐1 sensitivity, and finally remarkably inhibit tumor growth in the mouse orthotopic BCa model. Thus, this study presents a novel intravesical delivery platform for ICB antibodies and a smart adjuvant system to achieve potent synergy immunotherapy, which is promising for bladder‐preserving treatment against BCa.

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Drug Repurposing in Cancer Therapy

Sen,

Kushwah,

Ranjan

2024

Drug Repurposing

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Drug Repurposing Flubendazole to Suppress Tumorigenicity via PCSK9-dependent Inhibition and Potentiate Lenvatinib Therapy for Hepatocellular Carcinoma

Cited by 10 publications

References 69 publications

Flubendazole presents anti-tumor effects by promoting cell cycle arrest and inhibiting the invadopodia in pancreatic cancer

Flubendazole presents anti-tumor effects by promoting cell cycle arrest and inhibiting the invadopodia in pancreatic cancer

Fluorinated Chitosan‐Mediated Transepithelial Delivery of Intravesical Dual‐Drug Immunotherapeutic for Bladder Cancer Therapy

Drug Repurposing in Cancer Therapy

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