Theranostics 2019; 9(15):4391-4408. doi:10.7150/thno.32462 This issue Cite

Research Paper

ZnAs@SiO2 nanoparticles as a potential anti-tumor drug for targeting stemness and epithelial-mesenchymal transition in hepatocellular carcinoma via SHP-1/JAK2/STAT3 signaling

Yongquan Huang1,2,3#, Bin Zhou2,3#, Hui Luo3#, Junjie Mao2,3, Yin Huang2, Ke Zhang2,3, Chaoming Mei3, Yan Yan3, Hongjun Jin3, Jinhao Gao4, Zhongzhen Su1,3, Pengfei Pang2,3✉, Dan Li3✉, Hong Shan2,3✉

1. Department of Ultrasound, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province 519000, China
2. Center for Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province 519000, China
3. Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province 519000, China
4. State Key Laboratory of Physical Chemistry of Solid Surfaces, The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, The Key Laboratory for Chemical Biology of Fujian Province, and Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian Province 361005, China
# These authors contributed equally to this article.

Citation:
Huang Y, Zhou B, Luo H, Mao J, Huang Y, Zhang K, Mei C, Yan Y, Jin H, Gao J, Su Z, Pang P, Li D, Shan H. ZnAs@SiO2 nanoparticles as a potential anti-tumor drug for targeting stemness and epithelial-mesenchymal transition in hepatocellular carcinoma via SHP-1/JAK2/STAT3 signaling. Theranostics 2019; 9(15):4391-4408. doi:10.7150/thno.32462. https://www.thno.org/v09p4391.htm
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Abstract

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Rationale: Current therapies for hepatocellular carcinoma (HCC) are hampered by treatment failure and recurrence due to the remaining treatment-resistant liver cancer stem cells (CSCs). Stemness and epithelial-mesenchymal transition (EMT) are regarded as two fundamental characteristics of liver CSCs necessary for cancer progression; thus, drugs that simultaneously target both characteristics should prove effective in eliminating HCC and impeding recurrence. In this study, we developed new arsenic trioxide (ATO)-based nanoparticles (NPs), which are expected to be more effective than the current HCC therapy, and explored their potential mechanism.

Methods: A “one-pot” reverse emulsification approach was employed to prepare the ZnAs@SiO2 NPs. HCC cell lines, MHCC97L and Hep3b, were used to analyze the antitumor activity of ZnAs@SiO2 NPs in vitro and in vivo by quantifying cell growth and metastasis as well as to study the effect on stemness and EMT. SHP-1 siRNA was used to validate the role of the SHP-1/JAK2/STAT3 signaling pathway in mediating inhibition of stemness and EMT by ZnAs@SiO2.

Results: Compared with the current ATO treatment, ZnAs@SiO2 NPs promoted apoptosis and significantly inhibited proliferation, migration, and invasion of both MHCC97L and Hep3b cells. In the in vivo assay, ZnAs@SiO2 NPs inhibited tumor growth by 2.2-fold and metastasis by 3.5-fold as compared to ATO. The ZnAs@SiO2 NPs also inhibited tumor spheroid formation in vitro and tumor initiation in vivo and induced significant changes in the expression of stemness markers (CD133, Sox-2, and Oct-4) and EMT markers (E-cadherin, Vimentin, and Slug) both in vitro and in vivo. These effects of ZnAs@SiO2 that correlated with prognosis of HCC were mediated by the SHP-1/JAK2/STAT3 signaling.

Conclusions: ZnAs@SiO2 NPs can effectively suppress tumor initiation, growth, metastasis, and inhibit stemness and EMT through regulation of SHP-1/JAK2/STAT3 signaling pathway in liver cancer cells in vitro and in vivo. Thus, ZnAs@SiO2 NPs have immense potential for HCC treatment in the future.

Keywords: Arsenic trioxide nanoparticles, stemness, epithelial-mesenchymal transition, hepatocellular carcinoma, SHP-1


Citation styles

APA
Huang, Y., Zhou, B., Luo, H., Mao, J., Huang, Y., Zhang, K., Mei, C., Yan, Y., Jin, H., Gao, J., Su, Z., Pang, P., Li, D., Shan, H. (2019). ZnAs@SiO2 nanoparticles as a potential anti-tumor drug for targeting stemness and epithelial-mesenchymal transition in hepatocellular carcinoma via SHP-1/JAK2/STAT3 signaling. Theranostics, 9(15), 4391-4408. https://doi.org/10.7150/thno.32462.

ACS
Huang, Y.; Zhou, B.; Luo, H.; Mao, J.; Huang, Y.; Zhang, K.; Mei, C.; Yan, Y.; Jin, H.; Gao, J.; Su, Z.; Pang, P.; Li, D.; Shan, H. ZnAs@SiO2 nanoparticles as a potential anti-tumor drug for targeting stemness and epithelial-mesenchymal transition in hepatocellular carcinoma via SHP-1/JAK2/STAT3 signaling. Theranostics 2019, 9 (15), 4391-4408. DOI: 10.7150/thno.32462.

NLM
Huang Y, Zhou B, Luo H, Mao J, Huang Y, Zhang K, Mei C, Yan Y, Jin H, Gao J, Su Z, Pang P, Li D, Shan H. ZnAs@SiO2 nanoparticles as a potential anti-tumor drug for targeting stemness and epithelial-mesenchymal transition in hepatocellular carcinoma via SHP-1/JAK2/STAT3 signaling. Theranostics 2019; 9(15):4391-4408. doi:10.7150/thno.32462. https://www.thno.org/v09p4391.htm

CSE
Huang Y, Zhou B, Luo H, Mao J, Huang Y, Zhang K, Mei C, Yan Y, Jin H, Gao J, Su Z, Pang P, Li D, Shan H. 2019. ZnAs@SiO2 nanoparticles as a potential anti-tumor drug for targeting stemness and epithelial-mesenchymal transition in hepatocellular carcinoma via SHP-1/JAK2/STAT3 signaling. Theranostics. 9(15):4391-4408.

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