Dasabuvir suppresses esophageal squamous cell carcinoma growth in vitro and in vivo through targeting ROCK1

Liu, Xinning; Jiang, Yanan; Zhou, Hao; Zhao, Xiaokun; Li, Mingzhu; Bao, Zhuo; Wang, Zitong; Zhang, Chenyang; Xie, Zhenliang; Zhao, Jimin; Dong, Zigang; Liu, Kangdong; Guo, Zhiping

doi:10.1038/s41419-023-05633-2

Cited by 4 publications

(2 citation statements)

References 53 publications

(57 reference statements)

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“…The application of FDA-approved drugs for cancer treatment has been a hotspot for studying pharmacokinetics, establishing safety in humans, and evaluating toxicity 31 , 32 . Consequently, it may be an intriguing strategy to utilize FDA-approved drugs for ESCC treatment, and several drugs have been demonstrated to have anti-cancer effect in ESCC, such as dasabuvir 48 (for hepatitis C virus treatment), azelnidipine 49 (for hypertension), penfluridol 50 (an antipsychotic drug), and antitussive 51 (an antitussive agent). In this study, we identified an FDA-approved drug, dexrazoxane, as a potential anti-cancer drug for ESCC both in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Dexrazoxane inhibits the growth of esophageal squamous cell carcinoma by attenuating SDCBP/MDA-9/syntenin-mediated EGFR-PI3K-Akt pathway activation

Du,

Xiao,

Han

et al. 2024

Sci Rep

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Syndecan-binding protein (SDCBP) was reported to stimulate the advancement of esophageal squamous cell carcinoma (ESCC) and could potentially be a target for ESCC treatment. There is a growing corpus of research on the anti-tumor effects of iron chelators; however, very few studies have addressed the involvement of dexrazoxane in cancer. In this study, structure-based virtual screening was employed to select drugs targeting SDCBP from the Food and Drug Administration (FDA)-approved drug databases. The sepharose 4B beads pull-down assay revealed that dexrazoxane targeted SDCBP by interacting with its PDZ1 domain. Additionally, dexrazoxane inhibited ESCC cell proliferation and anchorage-independent colony formation via SDCBP. ESCC cell apoptosis and G2 phase arrest were induced as measured by the flow cytometry assay. Subsequent research revealed that dexrazoxane attenuated the binding ability between SDCBP and EGFR in an immunoprecipitation assay. Furthermore, dexrazoxane impaired EGFR membrane localization and inactivated the EGFR/PI3K/Akt pathway. In vivo, xenograft mouse experiments indicated that dexrazoxane suppressed ESCC tumor growth. These data indicate that dexrazoxane might be established as a potential anti-cancer agent in ESCC by targeting SDCBP.

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Section: Discussionmentioning

confidence: 99%

Dexrazoxane inhibits the growth of esophageal squamous cell carcinoma by attenuating SDCBP/MDA-9/syntenin-mediated EGFR-PI3K-Akt pathway activation

Du,

Xiao,

Han

et al. 2024

Sci Rep

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“…The dosage of 5-Fu that was used in this study was based on our published article 21 . The dosage of DSV was selected according to a published article and our preliminary experiment 46 . For each animal, three different investigators were involved: two investigators (S.H.…”

Section: Methodsmentioning

confidence: 99%

Dasabuvir alleviates 5-fluorouracil-induced intestinal injury through anti-senescence and anti-inflammatory

He,

Wang,

Xia

et al. 2024

Sci Rep

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Abstract5-Fluorouracil (5-Fu) is a basic drug that is used to treat colorectal cancer. Patients who receive 5-Fu chemotherapy often experience side effects that affect the digestive system, such as intestinal injury and diarrhoea, which significantly affect patient compliance with anticancer treatment and quality of life. Therefore, identifying approaches to treat or prevent these side effects is urgent. Dasabuvir (DSV) is a hepatitis C virus inhibitor, but its impact on 5-Fu-induced intestinal injury remains unknown. Our study investigated the effects of DSV on 5-Fu-induced intestinal injury in HUVECs, HIECs and male BALB/c mice. We found that 5-Fu caused intestinal damage by inducing senescence, increasing inflammatory factor expression, and generating oxidative stress. Compared with 5-Fu treatment alone, DSV inhibited senescence by reducing senescence-β-galactosidase (SA-β-gal) activity, the senescence-associated secretory phenotype (SASP, including IL-1, IL-6, and TNF-α) and senescence marker expression levels (p16, p21, and p53). Moreover, the anti-senescence effect of DSV was achieved by inhibiting the mTOR signaling pathway. DSV increased antioxidant enzyme levels and alleviated intestinal tissue injury in mice. In addition, DSV suppressed the 5-Fu-induced increase the diarrhoea scores and ameliorated the weight loss, food intake and water intake of the mice. Overall, this study indicated that DSV could be used to treat chemotherapy-induced intestinal damage.

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Structure-based virtual screening of ROCK1 inhibitors for the discovery of Enterovirus-A71 antivirals

Qiao,

Tang,

et al. 2023

Virology

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Dasabuvir suppresses esophageal squamous cell carcinoma growth in vitro and in vivo through targeting ROCK1

Cited by 4 publications

References 53 publications

Dexrazoxane inhibits the growth of esophageal squamous cell carcinoma by attenuating SDCBP/MDA-9/syntenin-mediated EGFR-PI3K-Akt pathway activation

Dexrazoxane inhibits the growth of esophageal squamous cell carcinoma by attenuating SDCBP/MDA-9/syntenin-mediated EGFR-PI3K-Akt pathway activation

Dasabuvir alleviates 5-fluorouracil-induced intestinal injury through anti-senescence and anti-inflammatory

Structure-based virtual screening of ROCK1 inhibitors for the discovery of Enterovirus-A71 antivirals

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