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Published on: December 1, 2016
Rhein shows potent efficacy against non-small-cell lung cancer through inhibiting the STAT3 pathway
Lehe Yang1,2,3, Jifa Li1, Lingyuan Xu1,2,3
1Department of Respiratory Medicine, Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325600, People's Republic of China, zhaochengguang@wmu.edu.cn, 873331666@qq.com.
Background:
Non-small-cell lung cancer (NSCLC) comprises about 85% of all lung cancers and is usually diagnosed at an advanced stage with poor prognosis. The IL-6/STAT3 signaling pathway plays a pivotal role in NSCLC biology. Rhein is a lipophilic anthraquinone extensively found in medicinal herbs. Emerging evidence suggests that Rhein has significant antitumor effects, supporting the potential uses of Rhein as an antitumor agent.
Methods:
Cell viability and colony formation were performed to examine Rhein's potent anti-proliferative effect in human NSCLC cell lines PC-9, H460 and A549. Flow cytometry-based assay was employed to study whether Rhein could affect cell apoptosis and cycle. The expression level of P-STAT3, apoptosis and cycle-related proteins Bcl-2, Bax, MDM2, CDC2, P53 and CyclinB1 were detected by Western blotting. The xenograft models were used to evaluate the in vivo effect of Rhein.
Results:
We found that Rhein could significantly reduce the viability and stimulate apoptosis in human NSCLC cells in a dose-dependent manner. Western blot analysis results suggested that the antitumor effect of Rhein might be mediated via STAT3 inhibition. Rhein upregulated the expression of the proapoptotic protein Bax and downregulated the expression of the antiapoptotic protein Bcl-2. In addition, Rhein induced the arrest of NSCLC cells in the G2/M phase of the cell cycle and dose dependently inhibited the expression of cycle-related proteins. The Rhein also inhibited tumor growth in H460 xenograft models.
Conclusion:
Rhein shows potent efficacy against NSCLC through inhibiting the STAT3 pathway. Our results also suggest that Rhein has a promising potential to be used as a novel antitumor agent for the treatment of NSCLC.
Insights
Rhein effectively combats non-small-cell lung cancer (NSCLC) by inhibiting the IL-6/STAT3 pathway, showing promise as a novel antitumor agent.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Non-small-cell lung cancer (NSCLC) is a prevalent cancer with poor prognosis, often diagnosed at advanced stages.
- The Interleukin-6/Signal Transducer and Activator of Transcription 3 (IL-6/STAT3) pathway is crucial in NSCLC development.
- Rhein, a natural compound from medicinal herbs, exhibits potential antitumor properties.
Purpose of the Study:
- To investigate the anti-proliferative and pro-apoptotic effects of Rhein on NSCLC.
- To elucidate the mechanism of Rhein's action, focusing on the IL-6/STAT3 pathway.
- To evaluate the in vivo efficacy of Rhein in NSCLC models.
Main Methods:
- Assessed Rhein's impact on NSCLC cell viability, colony formation, apoptosis, and cell cycle progression using cell-based assays.
- Analyzed protein expression levels of STAT3, apoptosis regulators (Bcl-2, Bax), and cell cycle proteins (MDM2, CDC2, P53, CyclinB1) via Western blotting.
- Evaluated Rhein's anti-tumor effect in vivo using NSCLC xenograft models.
Main Results:
- Rhein significantly reduced NSCLC cell viability and induced apoptosis in a dose-dependent manner.
- Rhein inhibited STAT3 phosphorylation, upregulated Bax, and downregulated Bcl-2 expression.
- Rhein caused G2/M cell cycle arrest and inhibited tumor growth in xenograft models.
Conclusions:
- Rhein demonstrates potent anti-NSCLC activity by inhibiting the STAT3 signaling pathway.
- Rhein effectively suppresses NSCLC proliferation and induces apoptosis.
- Rhein holds promise as a potential novel therapeutic agent for NSCLC treatment.
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