Exploring the Relationship Between Autophagy and Gefitinib Resistance in NSCLC by Silencing PDLIM5 Using Ultrasound-targeted Microbubble Destruction Technology

Overview

Journal Cancer Cell Int

Publisher Biomed Central

Date 2022 Sep 26

PMID 36154921

Authors

Yao Zhang

Wenhao Lv

Hui Li

Tiantian Dong

Hao Wu

Chunhong Su

Hong Shu

Fang Nie

Affiliations

Soon will be listed here.

Abstract

Background: Ultrasound-targeted microbubble destruction (UTMD) technology is a new drug and gene delivery strategy. This study investigates novel ultrasound (US) sensitive siRNA-loaded nanobubbles (siRNA-NBs) to explore the relationship between PDLIM5 mediated autophagy and drug resistance development using epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of non-small cell lung cancer (NSCLC).

Methods: US sensitive siRNA-NBs were designed to inhibit the expression of PDLIM5 in gefitinib-resistant human NSCLC PC9GR cells in vitro. The expression of autophagy-related proteins (P62 and LC3-II/I) and autophagosomes in PC9GR cells after PDLIM5 gene silencing were explored.

Results: US-sensitive PDLIM5-targeted siRNA-NBs were effectively delivered into PC9GR cells, inhibiting PDLIM5 expression, increasing LC3-II/I and p62 expressions and increasing autophagosomes in PC9GR cells in vitro.

Conclusions: Using UTMD, US-sensitive siRNA-NBs have the potential as an ideal delivery vector to mediate highly effective RNA interference for NSCLC cells. Furthermore, PDLIM5 plays a role in the autophagy-mediated resistance in gefitinib-resistant PC9GR cells.

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