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| Status |
Public on Aug 30, 2024 |
| Title |
Thioridazine reverses trastuzumab resistance in gastric cancer by inhibiting S-phase kinase associated protein 2-mediated aerobic glycolysis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Trastuzumab constitutes the fundamental component of initial therapy for patients with advanced human epidermal growth factor receptor 2 (HER-2)- positive gastric cancer (GC). However, the efficacy of this treatment is hindered by substantial challenges associated with both primary and acquired drug resistance. While S-phase kinase associated protein 2 (Skp2) overexpression has been implicated in the malignant progression of GC, its role in regulating trastuzumab resistance in this context remains uncertain. Despite the numerous studies investigating Skp2 inhibitors among small molecule compounds and natural products, there has been a lack of successful commercialization of drugs specifically targeting Skp2.To discover a Skp2 blocker among currently available medications and develop a therapeutic strategy for HER2- positive GC patients who have experienced progression following trastuzumab-based treatment.
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| Overall design |
Skp2 exogenous overexpression plasmids and small interfering RNA vectors were utilized to investigate the correlation between Skp2 expression and trastuzumab resistance in GC cells. Q-PCR, western blot, and immunohis- tochemical analyses were conducted to evaluate the regulatory effect of thioridazine on Skp2 expression. A cell counting kit-8 assay, flow cytometry, a amplex red glucose/glucose oxidase assay kit, and a lactate assay kit were utilized to measure the proliferation, apoptosis, and glycolytic activity of GC cells in vitro. A xenograft model established with human GC in nude mice was used to assess thioridazine's effectiveness in vivo
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| Citation(s) |
39174739 |
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| Submission date |
Jul 18, 2024 |
| Last update date |
Aug 30, 2024 |
| Contact name |
yiwei zhao |
| E-mail(s) |
zhaoyiwei97@outlook.com
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| Phone |
18737816831
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| Organization name |
河南大学抗体药物开发技术国家地方联合工程实验室
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| Street address |
河南大学金明校区
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| City |
开封 |
| ZIP/Postal code |
475100 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA1137397 |
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