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125I seed implantation enhances arsenic trioxide-induced apoptosis and anti-angiogenesis in lung cancer xenograft mice

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Abstract

Background and Purpose

Arsenic trioxide (ATO) exerts anticancer effects on lung cancer. However, the clinical use of ATO is limited due to its systemic toxicity and resistance of lung cancer cells. The present study aimed to investigate the effects of ATO, alone and in combination with 125I seed implantation on tumor growth and proliferation in lung cancer xenograft mice, and investigate the possible molecular mechanisms.

Methods

The transmission electron microscope observed the tumor ultrastructure of lung cancer xenograft mice. The proliferation index of Ki-67 and the number and morphology of tumor microvessels were detected with immunohistochemical staining. The protein and mRNA expression were examined by western blot and real-time PCR assay.

Results

The in vivo results demonstrated that ATO combined with 125I seed significantly inhibited tumor growth and proliferation, as well as promoted apoptosis, and decreased the Ki-67 index and microvessel density in lung cancer xenograft mice. Moreover, ATO combined with 125I seed decreased the protein and mRNA expression levels of HIF-1α, VEGF, and BCL-2, and increased those of BAX and P53.

Conclusions

ATO combined with 125I seed significantly inhibited tumor growth and proliferation in lung cancer, which may be accomplished by inhibiting tumor angiogenesis and inducing apoptosis.

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Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank the Department of Pharmacy of the Second Affiliated Hospital of Xi'an Jiaotong University for providing arsenic trioxide and the 125I seeds provided by the Seed Therapy Center of Tumor Hospital of Shaanxi Province.

Funding

This project is supported by the China Postdoctoral Science Foundation (grant no. 2020M683511), Shaanxi Province key research and development program (grant no. 2022SF-261) and Incubation Project of National Natural Science Foundation of Tumor Hospital of Shaanxi Province (grant no. SC221107).

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Author notes

  1. Guang-Yan Lei and Le Han have contributed equally to this work.

Authors and Affiliations

  1. Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi’an Jiaotong University, 309 Yanta West Road, Xi’an, 710061, Shaanxi, People’s Republic of China

    Zheng-Hong Chen, Yi-Li Zhang, Bin Yuan & Wen-Juan Chen

  2. Department of Thoracic Surgery and Seed Therapy Center, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi’an Jiaotong University, 309 Yanta West Road, Xi’an, 710061, Shaanxi, People’s Republic of China

    Guang-Yan Lei & Le Han

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  1. Zheng-Hong Chen
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Correspondence to Guang-Yan Lei or Le Han.

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This study was approved by the Ethics Committee of the Experimental Animal of the Shaanxi University of Chinese Medicine (SUCMDL20191025001).

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Chen, ZH., Zhang, YL., Yuan, B. et al. 125I seed implantation enhances arsenic trioxide-induced apoptosis and anti-angiogenesis in lung cancer xenograft mice. Clin Transl Oncol 25, 2127–2137 (2023). https://doi.org/10.1007/s12094-023-03092-x

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