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Rhein Shows Potent Efficacy Against Non-Small-Cell Lung Cancer Through Inhibiting the STAT3 Pathway

Rhein Shows Potent Efficacy Against Non-Small-Cell Lung Cancer Through Inhibiting the STAT3 Pathway

Lehe Yang, Jifa Li, Lingyuan Xu, Shichong Lin, Youqun Xiang, Xuanxuan Dai, Guang Liang, Xiaoying Huang, Jiandong Zhu, Chengguang Zhao

Cancer Manag Res. 2019 Feb 1;11:1167-1176.

PMID: 30774444

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP478433-A	Rhein		478-43-3	Price

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