Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Apr 15, 2024; 16(4): 1437-1452
Published online Apr 15, 2024. doi: 10.4251/wjgo.v16.i4.1437
Curcumin inhibits the growth and invasion of gastric cancer by regulating long noncoding RNA AC022424.2
Bin-Sheng Wang, Chen-Li Zhang, Xiang Cui, Qiang Li, Lei Yang, Zhi-Yun He, Ze Yang, Miao-Miao Zeng, Nong Cao
Bin-Sheng Wang, Xiang Cui, Lei Yang, Zhi-Yun He, Ze Yang, Miao-Miao Zeng, Nong Cao, Department of General Surgery, First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
Chen-Li Zhang, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, Gansu Province, China
Qiang Li, Third Department of General Surgery, First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
Author contributions: Wang BS, Cui X, and Zhang CL performed the experiments and image acquisition; Wang BS, Cui X, Zhang CL, Li Q, Yang Z, Yang L, and He ZY designed the study and wrote the manuscript; Wang BS, Yang Z, and Cao N edited the manuscript.
Supported by the Natural Science Foundation of Gansu Province, China, No. 20JR5RA356 and No. 22JR5RA511; and the Lanzhou City Chengguan District Science and Technology Planning Project, No. 2016-7-17.
Institutional review board statement: This study was approved by the Ethics Committee of the First Hospital of Lanzhou University.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: The datasets used and/or analyzed during this study are available from the corresponding author upon reasonable request.
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 Non-Commercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Nong Cao, MD, Professor, Department of General Surgery, First Hospital of Lanzhou University, No. 1 Donggang West Road, Lanzhou 730000, Gansu Province, China. caonongldyy@126.com
Received: October 13, 2023
Peer-review started: October 13, 2023
First decision: December 8, 2023
Revised: December 19, 2023
Accepted: January 17, 2024
Article in press: January 17, 2024
Published online: April 15, 2024
Abstract
BACKGROUND

Gastric cancer, characterized by a multifactorial etiology and high heterogeneity, continues to confound researchers in terms of its pathogenesis. Curcumin, a natural anticancer agent, exhibits therapeutic promise in gastric cancer. Its effects include promoting cell apoptosis, curtailing tumor angiogenesis, and enhancing sensitivity to radiation and chemotherapy. Long noncoding RNAs (lncRNAs) have garnered significant attention as biomarkers for early screening, diagnosis, treatment, and drug response because of their remarkable specificity and sensitivity. Recent investigations have revealed an association between aberrant lncRNA expression and early diagnosis, clinical staging, metastasis, drug sensitivity, and prognosis in gastric cancer. A profound understanding of the intricate mechanisms through which lncRNAs influence gastric cancer development can provide novel insights for precision treatment and tailored management of patients with gastric cancer. This study aimed to unravel the potential of curcumin in suppressing the malignant behavior of gastric cancer cells by upregulating specific lncRNAs and modulating gastric cancer onset and progression.

AIM

To identify lncRNAs associated with curcumin treatment and investigate the role of lncRNA AC022424.2 in the effects of curcumin on gastric cancer cell apoptosis, proliferation, and invasion. Furthermore, these findings were validated in clinical samples.

METHODS

The study employed CCK-8 assays to assess the impact of curcumin on gastric cancer cell proliferation, flow cytometry to investigate its effects on apoptosis, and scratch and Transwell assays to evaluate its influence on the migration and invasion of BGC-823 and MGC-803 cells. Western blotting was used to gauge changes in the protein expression levels of CDK6, CDK4, Bax, Bcl-2, caspase-3, P65, and the PI3K/Akt/mTOR pathway in gastric cancer cell lines after curcumin treatment. Differential expression of lncRNAs before and after curcumin treatment was assessed using lncRNA sequencing and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in BGC-823 and MGC-803 cells. AC022424.2-1 knockdown BGC-823 and MGC-803 cells were generated to scrutinize the impact of lncRNA AC022424.2 on apoptosis, proliferation, migration, and invasion of gastric cancer cells. Western blotting was performed to ascertain changes in the expression of proteins implicated in the PI3K/Akt/mTOR and NF-κB signaling pathways. RT-PCR was employed to measure lncRNA AC022424.2 expression in clinical gastric cancer tissues and to correlate its expression with clinical pathological characteristics.

RESULTS

Curcumin induced apoptosis and hindered proliferation, migration, and invasion of gastric cancer cells in a dose- and time-dependent manner. LncRNA AC022424.2 was upregulated after curcumin treatment, and its knockdown enhanced cancer cell aggressiveness. LncRNA AC022424.2 may have affected cancer cells via the PI3K/Akt/mTOR and NF-κB signaling pathways. LncRNA AC022424.2 downregulation was correlated with lymph node metastasis, making it a potential diagnostic and prognostic marker.

CONCLUSION

Curcumin has potential anticancer effects on gastric cancer cells by regulating lncRNA AC022424.2. This lncRNA plays a significant role in cancer cell behavior and may have clinical implications in diagnosis and prognosis evaluation. The results of this study enhance our understanding of gastric cancer development and precision treatment.

Keywords: Gastric cancer, Curcumin, Long noncoding RNA AC022424.2, Apoptosis, Akt/PI3K pathway, Lymph metastasis

Core Tip: We investigated the effects of curcumin on gastric cancer cells, and we found that curcumin inhibited gastric cancer cell growth and induced apoptosis via long noncoding RNA (lncRNA) AC022424.2. Furthermore, the AKT and mTOR signaling pathways were involved in the process. We validated the role of lncRNA AC022424.2 on clinical samples and found that lncRNA AC022424.2 is associated with lymph metastasis.