Resveratrol Inhibition of Renal Cancer Stem Cell Characteristics and Modulation of the Sonic Hedgehog Pathway

Abstract

Aims

Renal cell cancers typically exhibit high metastasis and recurrence, and this is thought to be due to renal cancer stem cells (CSCs). Meanwhile, aberrant activation of Sonic hedgehog (Shh) signaling is linked with CSCs. Resveratrol has direct or indirect impacts on the pathological activities of CSCs. However, the effects of resveratrol on renal CSCs remain to be elucidated.

Methods

We cultured renal CSCs in serum-free medium. Western blotting was used to analyze the expression levels of related proteins. The mRNA changes were detected by qRT-PCR after resveratrol treatment. The CD133⁺ cells were quantified by flow cytometry analysis. Immunofluorescence staining images showed the changes in CD44 and Smoothened expression in the cell spheres.

Results

Renal CSCs were enriched by tumorsphere formation assays of ACHN and 786-O cells. Resveratrol treatments markedly decreased the size and number of cell spheres and downregulated the expression of the Shh pathway-related proteins and CSCs markers. Moreover, we observed that resveratrol inhibited cell proliferation and induced cell apoptosis, while purmorphamine upregulated the Shh pathway and weakened the effects of resveratrol on renal CSCs.

Conclusions

These results suggested that resveratrol is a potential novel therapeutic agent that targets inactivation of renal CSCs by affecting the function of the Shh pathway.

Disclosure Statement

No potential conflict of interest was reported by the author(s).

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Author Contributions

Hongliang Sun: Acquisition of data, analysis of data, drafting the article. Taotao Zhang: Acquisition of data. Rui Liu: Acquisition of data. Wanshuang Cao: Analysis of data. Zhiqiang Zhang: Revising the article. Zhiqi Liu: Revising the article. Weiwei Qian: Revising the article, supervision. Dengdian Wang: Revising the article, supervision. Dexin Yu: Conception and design, final approval of the version to be published. Caiyun Zhong: Conception and design, final approval of the version to be published, acquisition of funding.

Additional information

Funding

This work was supported by grants from the National Natural Science Foundation of China (No. 81773431) and by the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine). This study was also supported by Key projects of Natural Science Foundation of Colleges and Universities in Anhui Province (KJ2018A0205).