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Cisplatin plus norcantharidin alter the expression of TGF-β1/Smads signaling pathway in hepatocellular carcinoma
Purpose:
To investigate the effects of cisplatin plus norcantharidin on transforming growth factor (TGF)-β1/Smads signaling pathway in hepatocellular carcinoma cells.
Methods:
Hepatocellular carcinoma cells (Hep3B) were divided into four groups: control group, cisplatin 2.0 μg/ml group, norcantharidin 10 μg/ml group, and cisplatin 2.0 μg/ml plus norcantharidin 10 μg/ml group. All cells were incubated for 24 hours. Cells proliferation was assessed using cell counting kit-8. Relative mRNA expression of TGF-β1, Smad4 and Smad7 were assessed by quantitative RT-PCR. Protein expression of TGF-β1 and Smad4 were investigated by western blotting.
Results:
Cisplatin, norcantharidin and cisplatin plus norcantharidin significantly inhibited the proliferation of cells, significantly attenuated both the mRNA and protein expression of TGF-β1 and Smad7, and significantly up-regulated the mRNA and protein expression of Smad4 in Hep3B (all p < 0.05), and cisplatin plus norcantharidin exhibited powerful effects than cisplatin and norcantharidin.
Conclusions:
Cisplatin, norcantharidin and cisplatin plus norcantharidin can significantly alter the expression of TGF-β1/Smads signaling pathway and inhibit the proliferation of Hep3B cells. Cisplatin plus norcantharidin exhibited powerful effects than cisplatin and norcantharidin (Fig. 4, Ref. 23).
Insights
Cisplatin and norcantharidin inhibit hepatocellular carcinoma cell proliferation by altering the transforming growth factor-beta 1 (TGF-β1)/Smads pathway. Combination therapy showed superior efficacy compared to monotherapy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Hepatocellular carcinoma (HCC) remains a significant global health challenge.
- The transforming growth factor-beta (TGF-β) signaling pathway plays a crucial role in HCC development and progression.
- Targeting the TGF-β1/Smads pathway presents a potential therapeutic strategy for HCC.
Purpose of the Study:
- To investigate the combined effects of cisplatin and norcantharidin on the TGF-β1/Smads signaling pathway in HCC cells.
- To evaluate the impact of these agents on hepatocellular carcinoma cell proliferation.
Main Methods:
- Hepatocellular carcinoma cells (Hep3B) were treated with cisplatin, norcantharidin, or a combination.
- Cell proliferation was assessed using the cell counting kit-8 assay.
- Messenger RNA (mRNA) and protein expression levels of TGF-β1, Smad4, and Smad7 were analyzed using quantitative RT-PCR and western blotting, respectively.
Main Results:
- Both cisplatin and norcantharidin, individually and in combination, significantly inhibited Hep3B cell proliferation.
- Treatment with these agents significantly attenuated the mRNA and protein expression of TGF-β1 and Smad7.
- The expression of Smad4 was significantly upregulated at both mRNA and protein levels by the treatments.
- The combination of cisplatin and norcantharidin demonstrated more potent effects than either agent alone.
Conclusions:
- Cisplatin and norcantharidin effectively inhibit hepatocellular carcinoma cell proliferation.
- These drugs modulate the TGF-β1/Smads signaling pathway, impacting key components like TGF-β1, Smad4, and Smad7.
- The combination therapy of cisplatin plus norcantharidin exhibits enhanced efficacy in inhibiting HCC cell proliferation and altering TGF-β1/Smads signaling compared to monotherapy.
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