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Andrographis modulates cisplatin resistance in lung cancer via miR-155-5p/SIRT1 axis
Chong Pang1, Tengyue Zhang2, Yulong Chen1
1Department of Lung Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Lung Cancer Center, Tianjin, China.
Abstract:
Andrographis (Andro) has been identified as an anti-cancer herbal. This study was to explore its underlying regulatory routes regarding cisplatin (DDP) resistance in lung cancer. The impacts of Andro on cell viability in lung cancer cells and normal cells BEAS-2B were validated using CCK8 tests. Then, cell viability and apoptosis analysis was performed in the cells after DDP, Andro, or combined treatment. RT-qPCR was applied for evaluating miR-155-5p and SIRT1 mRNA expressions, while western blot was for evaluating SIRT1 protein expressions. Binding sites between SIRT1 and miR-155-5p were predicted on TargetScan and were confirmed using luciferase reporter assays. Xenograft animal models were established for in vivo validation of the regulatory function of Andro in lung cancer. Andro decreased the cell viability in lung cancer cells but not normal cells BEAS-2B. The combined treatment with DDP and Andro induced the lowest viability and highest apoptosis in both A549 and A549/DDP cells. MiR-155-5p expression was suppressed, and SIRT was promoted by the Andro treatment, while overexpression of miR-155-5p reversed effects of Andro in cells, which was further counteracted by SIRT1 activation. SIRT1 was verified to be a target of miR-155-5p in A549/DDP cells. Moreover, Andro synergized with DDP in mice with lung cancer via miR-155-5p/SIRT1. Andro modulates cisplatin resistance in lung cancer via miR-155-5p/SIRT1 axis.
Insights
Andrographis (Andro) combats cisplatin resistance in lung cancer by targeting the miR-155-5p/SIRT1 pathway. This herbal compound enhances chemotherapy effectiveness and reduces cancer cell viability.
Area of Science:
- Pharmacology
- Molecular Biology
- Oncology
Background:
- Cisplatin resistance is a major challenge in lung cancer treatment.
- Andrographis (Andro) exhibits anti-cancer properties.
- Understanding Andro's regulatory mechanisms in cisplatin resistance is crucial.
Purpose of the Study:
- To investigate the regulatory pathways of Andrographis (Andro) in overcoming cisplatin (DDP) resistance in lung cancer.
- To elucidate the role of the miR-155-5p/SIRT1 axis in Andro's anti-cancer effects.
Main Methods:
- Cell viability assays (CCK8) and apoptosis analysis were performed on lung cancer cells.
- RT-qPCR and Western blot were used to assess miR-155-5p and SIRT1 expression.
- Luciferase reporter assays confirmed the interaction between SIRT1 and miR-155-5p.
- Xenograft models were utilized for in vivo validation.
Main Results:
- Andro reduced lung cancer cell viability without affecting normal cells.
- Combined Andro and DDP treatment significantly decreased viability and increased apoptosis.
- Andro suppressed miR-155-5p and promoted SIRT1 expression, a relationship confirmed as a direct target interaction.
- In vivo studies demonstrated Andro's synergistic effect with DDP via the miR-155-5p/SIRT1 pathway.
Conclusions:
- Andrographis (Andro) effectively modulates cisplatin resistance in lung cancer.
- The miR-155-5p/SIRT1 axis is a key regulatory pathway for Andro's action.
- Andro holds potential as an adjuvant therapy to enhance cisplatin efficacy in lung cancer treatment.
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