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IGFBP-3 Is the Key Target of Sanguinarine in Promoting Apoptosis in Hepatocellular Carcinoma

Authors Wang H, Wang H, Li K, Li S, Sun B

Received 11 October 2019

Accepted for publication 11 January 2020

Published 11 February 2020 Volume 2020:12 Pages 1007—1015

DOI https://doi.org/10.2147/CMAR.S234291

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Bilikere Dwarakanath


Huiwen Wang,1,* He Wang,1,* Kai Li,1 Shijie Li,1 Bingyi Sun2

1Department of Interventional, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, People’s Republic of China; 2Department of General Surgery, The First Hospital of Qiqihar, Qiqihar 161005, Heilongjiang Province, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Bingyi Sun
Department of General Surgery, The First Hospital of Qiqihar (Equals to: Affiliated Qiqihar Hospital, Southern Medical University), Qiqihar 161005, Heilongjiang Province, People’s Republic of China
Email sunbingyi82@163.com

Introduction: Chemotherapeutic treatment of hepatocellular carcinoma (HCC) has always been plagued by nonspecific and side effects. Plant extracts have potential anticancer capabilities with low cytotoxicity and few side effects, but their detailed mechanisms are still unclear, thus limiting their clinical applications.
Methods: In this study, five plant extracts were chosen, their inhibition on HCC cell viability was compared by CCK-8 assay and sanguinarine (SAN) was selected. Then, wound healing assay, transwell assay, and apoptosis assay were carried out in Hep3B cells. Bioinformatics methods were performed and IGFBP-3 was predicted the targets of SAN in HCC. The mechanism of SAN regulating IGFBP-3 was explored using qRT-PCR, Western blotting, cell viability assay and apoptosis assay. Meanwhile, knockdown of IGFBP-3 were used by small interfering RNA (siRNA).
Results: In five plant extracts, SAN inhibited the proliferation of HCC cell lines most considerably. In addition, apoptosis was promoted, and invasion and migration were inhibited in the Hep3B cell line by treatment with SAN at 2 μM. Bioinformatics indicated that SAN could affect HCC apoptosis through the TP53/IGFBP-3 pathway, and further verification experiments showed that SAN upregulated the expression of insulin-like growth factor binding protein-3 (IGFBP-3) in the Hep3B cell line; SAN also inhibited the expression of Bcl-2 and promoted the expression of BAX and caspase-3. After using siRNA to inhibit the expression of IGFBP-3, the effect of SAN was blocked.
Conclusion: Our study further reveals a novel mechanism that IGFBP-3 is an important target of SAN, by upregulating expression of IGFBP-3, SAN promotes apoptosis in HCC.

Keywords: sanguinarine, IGFBP-3, apoptosis, hepatocellular carcinoma

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