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Daurisoline inhibits hepatocellular carcinoma progression by restraining autophagy and promoting cispaltin-induced cell death.

Abstract：

:Hepatocellular carcinoma (HCC) is a common malignancy with high cancer-associated mortality. Suppressing autophagy has been reported to promote the efficiency of chemotherapy in HCC. Daurisoline (DAS) is a constituent of Rhizoma Menispermi, and functions as a potential autophagy inhibitor to perform different cellular events. In the present study, we found that DAS treatment up-regulated autophagosomes in HCC cells, accompanied with the increases of LC3-II and p62, demonstrating the disturbance of autophagic flux. Then, by the colocalization analysis, we identified that DAS did not repress the fusion of autophagosomes and lysosomes in HCC cells. However, Lysotracker and acridine orange (OA) staining showed that DAS could suppress lysosomal acidification, as evidenced by the decreased red fluorescence. Consistently, significant decreases in mature form of cathepsin B and cathepsin D were detected in DAS-treated HCC cells. Furthermore, DAS treatment markedly promoted the anti-cancer effects of cisplatin (cDDP) on HCC cells, as revealed by the dramatically reduced cell viability and proliferation, whereas the enhanced apoptosis. Moreover, the nude mice xenograft models with HCC confirmed that compared with cDDP alone group, DAS combined with cDDP significantly reduced tumor progression in vivo. Taken together, these findings elucidated that DAS could restrain autophagic flux, potentiating the chemosensitivity of HCC cells to cDDP treatment.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Xue L,Liu P

doi

10.1016/j.bbrc.2020.09.068

subject

Has Abstract

pub_date

2021-01-01 00:00:00

pages

1083-1090

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(20)31815-5

journal_volume

534

pub_type

杂志文章

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