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Exosome-mediated delivery of SCD-1 siRNA promoted the death of anaplastic thyroid carcinoma cells via regulating ROS level

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Abstract

Purpose

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers in the world. Stearoyl-CoA desaturase-1 (SCD-1) is one of major enzymes in the de novo synthesis of fatty acids and is related to cancer aggressiveness and poor patient prognosis. The study aimed to construct exosomes loaded SCD-1 interference, investigate its effects and mechanisms on the cell proliferation and apoptosis of ATC cells.

Methods

The expressions of SCD-1 in normal thyroid cell line and ATC cell lines were determined by qRT-PCR and western blotting, respectively. Exosomes were prepared and purification then loaded with SCD-1 siRNA by electroporation and observed by transmission electron microscopy. Higher SCD-1 mRNA and protein levels were found in ATC cell lines compared than normal thyroid cell line (P < 0.05), and both Hth-7 and FRO cells could uptake PKH67-labeled exosomes. The effects of exosomes loaded SCD-1 siRNA on ATC cells were measured by CCK8 assay and apoptosis detection kit.

Results

When compared with control group, the cell viability significantly decreased in both two ATC cell lines taken up exosomes loaded SCD-1 siRNA (P < 0.001), and apoptotic and necrotic cells obviously increased (P < 0.05). In order to explore the mechanism of exosomes loaded SCD-1 on ATC, the ROS level was detected by fluorescence reagent. It was found that exosomes loaded SCD-1 siRNA significantly increased intracellular ROS level of ATC cells (P < 0.05).

Conclusions

Exosomes loaded SCD-1 siRNA inhibited ATC cellular proliferation and promoted cellular apoptosis, and the mechanisms involved maybe the regulation of fatty acids metabolism and ROS level. Our study provides a promising therapeutic strategy for ATC.

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Acknowledgements

The study was supported by grants from National Natural Science Foundation of China (No. 81873178), Key disciplines Construction Project of Pudong Health Burea of Shanghai (PWZxk2017-06), Natural Science Foundation of Shanghai Science and Technology Commission (No. 17ZR1421600), Excellent subject leader training project of the 3-year action plan of Shanghai public health system (No. GWV-10.2-XD15), and Key discipline construction project of the 3-year action plan of Shanghai public health system (GWV-10.1-XK9).

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Author notes

  1. M. Wang and Y. Ye authors have contributed equally to this work and should be considered as co-first authors.

Authors and Affiliations

  1. Department of Nuclear Medicine, The Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, 358 Datong Road, Pudong, Shanghai, 200137, People’s Republic of China

    M. H. Wang,  B. R. Zhou & W. Xia

  2. Central Laboratory, Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China

    Y. Ye, M. Zhang,  J. N. Wang &  Y. N. Song

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  1. M. H. Wang
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Contributions

WX and YS conceived the experiments. MW, MZ and BZ conducted the experiments. YY and JW analyzed the data. YS wrote the paper. WX and YY revised the paper. All authors read and approved the final manuscript.

Corresponding author

Correspondence to W. Xia.

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The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by Ethical Committee of Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine and conducted in accordance with the ethical standards.

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Wang, .H., Ye, Y., Zhang, M. et al. Exosome-mediated delivery of SCD-1 siRNA promoted the death of anaplastic thyroid carcinoma cells via regulating ROS level. Clin Transl Oncol 24, 288–296 (2022). https://doi.org/10.1007/s12094-021-02682-x

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