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Therapeutic delivery of microRNA-143 by cationic lipoplexes for non-small cell lung cancer treatment in vivo

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide and new improvements are urgently needed. Several miRNA-targeted therapeutics have reached clinical development. MicroRNA-143 (miR-143) was found to significantly suppress the migration and invasion of NSCLC. It might be of great potential for NSCLC treatment. However, the therapeutic effect of miR-143 against NSCLC in vivo has not been explored until now.

Methods

The cationic liposome/pVAX-miR-143 complex (CL-pVAX-miR-143) was prepared and its biodistribution was assessed. The tumor suppression effects of CL-pVAX-miR-143 were evaluated in early-stage and advanced experimental lung cancer metastasis mice models by systemic delivery, respectively, and also in subcutaneous tumor models by intratumoral injection. The toxicity of CL-pVAX-miR-143 was assessed by H&E analysis and biochemical measurements. The preliminary mechanism of CL-pVAX-miR-143 on tumor suppression was explored by immunochemistry and western blotting.

Results

The assays on the stability and safety of CL-pVAX-miR-143 showed that it mainly accumulated in the lung after systemic administration. The intratumoral delivery of CL-pVAX-miR-143 effectively inhibited A549 subcutaneous tumor growth. Notably, systemic delivery of CL-pVAX-miR-143 significantly inhibited tumor metastasis and prolonged survival dose dependently in early-stage experimental lung cancer metastasis models. More importantly, same results were shown in advanced mice models with metastasis. CL-pVAX-miR-143 treatment did not induce obvious acute toxicity. The preliminary mechanism on inhibiting tumor metastasis might be induced by targeting CD44v3.

Conclusions

Our results suggested that CL-pVAX-miR-143 might be a promising strategy for clinical treatment of non-small cell lung cancer, especially for advanced NSCLC with metastasis.

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Author notes

  1. Qianqian Jiang and Yue Yuan contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University/Collaborative Innovation Center of Biotherapy, No. 1, Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, Chengdu, 610041, Sichuan, China

    Qianqian Jiang, Yue Yuan, Yi Gong, Xinmei Luo, Xiaolan Su, Xueting Hu & Wen Zhu

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  1. Qianqian Jiang
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  2. Yue Yuan
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Correspondence to Wen Zhu.

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This article does not contain any studies with human participants performed by any of the authors. All experiments involving animals were admitted and performed according to the requirements of the Institutional Animal Care and Use Committee of West China Hospital, Sichuan University.

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Jiang, Q., Yuan, Y., Gong, Y. et al. Therapeutic delivery of microRNA-143 by cationic lipoplexes for non-small cell lung cancer treatment in vivo. J Cancer Res Clin Oncol 145, 2951–2967 (2019). https://doi.org/10.1007/s00432-019-03051-6

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