Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Sep 15, 2021; 13(9): 1164-1183
Published online Sep 15, 2021. doi: 10.4251/wjgo.v13.i9.1164
Scoparone inhibits pancreatic cancer through PI3K/Akt signaling pathway
Na Li, Fan Yang, Dong-Yan Liu, Jin-Tao Guo, Nan Ge, Si-Yu Sun
Na Li, Department of Hospice Care, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
Fan Yang, Jin-Tao Guo, Nan Ge, Si-Yu Sun, Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
Dong-Yan Liu, Medical Research Center, Shengjing Hospital of China Medical University, Benxi 111700, Liaoning Province, China
Author contributions: Li N and Sun SY conceived and designed the study; Li N performed the assays, analyzed and interpreted the data, and drafted the article; Yang F and Liu DY gave guidance and advice; Ge N and Guo JT revised the article for important intellectual content; all authors performed the final approval of the article.
Supported by National Natural Science Foundation of China, No. 817706555; Special Project from the Central Government of Liaoning Province, No. 2018107003; Liaoning Province Medical Science and Technology Achievements Transformation Foundation, No. 2018225120; China Postdoctoral Science Foundation, No. 2020M670101ZX; Doctoral Scientific Research Foundation of Liaoning Province, No. 2019-BS-276; Science and Technology Program of Shenyang, No. 19-112-4-103; Youth Support Foundation of China Medical University, No. QGZ2018058; Scientific Fund of Shengjing Hospital, No. 201801; and 345 Talent Project of Shengjing Hospital, No. 52-30C.
Institutional review board statement: The study was reviewed and approved by the Ethics Review Committee and Ethics Committee of Shengjing Hospital of China Medical University (No. 2020PS766K).
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Si-Yu Sun, MD, PhD, Chief Doctor, Doctor, Professor, Department of Gastroenterology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Shenyang 110004, Liaoning Province, China. sun-siyu@163.com
Received: March 4, 2021
Peer-review started: March 4, 2021
First decision: April 6, 2021
Revised: April 9, 2021
Accepted: July 5, 2021
Article in press: July 5, 2021
Published online: September 15, 2021
Processing time: 190 Days and 8.6 Hours
Abstract
BACKGROUND

Pancreatic cancer is a highly malignant tumor of the gastrointestinal system whose emerging resistance to chemotherapy has necessitated the development of novel antitumor treatments. Scoparone, a traditional Chinese medicine monomer with a wide range of pharmacological properties, has attracted considerable attention for its antitumor activity.

AIM

To explore the potential antitumor effect of scoparone on pancreatic cancer and the possible molecular mechanism of action.

METHODS

The target genes of scoparone were determined using both the bioinformatics and multiplatform analyses. The effect of scoparone on pancreatic cancer cell proliferation, migration, invasion, cell cycle, and apoptosis was detected in vitro. The expression of hub genes was tested using quantitative reverse transcription polymerase chain reaction (qRT-PCR), and the molecular mechanism was analyzed using Western blot. The in vivo effect of scoparone on pancreatic cancer cell proliferation was detected using a xenograft tumor model in nude mice as well as immunohistochemistry.

RESULTS

The hub genes involved in the suppression of pancreatic cancer by scoparone were obtained by network bioinformatics analyses using publicly available databases and platforms, including SwissTargetPrediction, STITCH, GeneCards, CTD, STRING, WebGestalt, Cytoscape, and Gepia; AKT1 was confirmed using qRT-PCR to be the hub gene. Cell Counting Kit-8 assay revealed that the viability of Capan-2 and SW1990 cells was significantly reduced by scoparone treatment exhibiting IC50 values of 225.2 μmol/L and 209.1 μmol/L, respectively. Wound healing and transwell assays showed that scoparone inhibited the migration and invasion of pancreatic cancer cells. Additionally, flow cytometry confirmed that scoparone caused cell cycle arrest and induced apoptosis. Scoparone also increased the expression levels of Bax and cleaved caspase-3, decreased the levels of MMP9 and Bcl-2, and suppressed the phosphorylation of Akt without affecting total PI3K and Akt. Moreover, compared with the control group, xenograft tumors, in the 200 μmol/L scoparone treatment group, were smaller in volume and lighter in weight, and the percentages of Ki65- and PCNA-positive cells were decreased.

CONCLUSION

Our findings indicate that scoparone inhibits pancreatic cancer cell proliferation in vitro and in vivo, inhibits migration and invasion, and induces cycle arrest and apoptosis in vitro through the PI3K/Akt signaling pathway.

Keywords: Pancreatic cancer; Scoparone; Akt1; PI3K/Akt signaling pathway; Bioinformatics analysis; Xenograft tumor

Core Tip: To explore the potential antitumor effect of scoparone on pancreatic cancer and the possible molecular mechanism, target genes of scoparone were determined using the bioinformatics and multiplatform analyses. The effect of scoparone on pancreatic cancer cell proliferation, migration, invasion, cell cycle, and apoptosis was detected. The expression of hub genes was detected using quantitative reverse transcription polymerase chain reaction, and Western blot was used to analyze the molecular mechanism. Xenograft tumor model and immunohistochemistry were used to detect cell proliferation in vivo. Our findings indicated that scoparone inhibits pancreatic cancer cell proliferation, migration, and invasion, and induced cell cycle arrest and apoptosis through the PI3K/Akt signaling pathway.