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Cancer-derived IgG involved in cisplatin resistance through PTP-BAS/Src/PDK1/AKT signaling pathway
Lu-Ming Wang1,2, Ye-Hua Gan1,2
1Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.
Objectives:
This study aimed to explore whether knockdown of cancer-derived IgG (CIgG) could enhance cisplatin-induced anti-cancer effects.
Materials And Methods:
Cancer-derived IgG was knocked down by siRNA or Tet-on shRNA in the absence or presence of cisplatin in WSU-HN6 or CAL27 cells. Cell proliferation, apoptosis, and mobility were evaluated using CCK-8, flow cytometry, and transwell assays, respectively. Molecular events were investigated using real-time PCR and Western blot assays.
Results:
Knockdown of CIgG significantly promoted cisplatin-induced apoptosis and inhibition of cell proliferation, migration, and invasion. Cisplatin upregulated CIgG expression and phosphorylation of AKT and PDK1, while knockdown of CIgG downregulated phosphorylation of AKT and PDK1, and blocked cisplatin-induced upregulation of AKT and PDK1 phosphorylation. Moreover, knockdown of CIgG blocked cisplatin-induced upregulation of Src phosphorylation, and knockdown of Src blocked cisplatin-induced upregulation of AKT and PDK1 phosphorylation. Overexpression of Src upregulated AKT and PDK1 phosphorylation. Furthermore, knockdown of CIgG upregulated PTP-BAS mRNA and protein expression, whereas cisplatin downregulated PTP-BAS protein, but not mRNA expression; knockdown of PTP-BAS upregulated phosphorylation of Src, PDK1, AKT, and blocked CIgG knockdown-mediated enhancement of cisplatin-induced inhibition of cell proliferation.
Conclusion:
Knockdown of CIgG enhanced the anti-cancer effects of cisplatin through PTP-BAS/Src/PDK1/AKT signaling pathway in oral squamous cell carcinoma.
Insights
Knocking down cancer-derived IgG (CIgG) enhances cisplatin
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Cancer-derived IgG (CIgG) plays a role in tumor progression.
- Cisplatin is a common chemotherapy agent with limited efficacy in some oral cancers.
Purpose of the Study:
- To investigate if CIgG knockdown potentiates cisplatin's anti-cancer effects.
- To elucidate the molecular mechanisms underlying this interaction in oral squamous cell carcinoma.
Main Methods:
- CIgG knockdown using siRNA and shRNA in oral cancer cell lines (WSU-HN6, CAL27).
- Assessment of cell proliferation, apoptosis, migration, and invasion.
- Analysis of molecular signaling pathways (AKT, PDK1, Src, PTP-BAS) via PCR and Western blot.
Main Results:
- CIgG knockdown significantly enhanced cisplatin-induced apoptosis and inhibited proliferation, migration, and invasion.
- CIgG knockdown reversed cisplatin-induced activation of the Src/PDK1/AKT pathway and modulated PTP-BAS expression.
- The PTP-BAS/Src/PDK1/AKT pathway is crucial for CIgG's influence on cisplatin efficacy.
Conclusions:
- CIgG knockdown is a promising strategy to enhance cisplatin's anti-cancer activity in oral squamous cell carcinoma.
- Targeting the PTP-BAS/Src/PDK1/AKT pathway may overcome cisplatin resistance.
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