Exploring the relationship between autophagy and Gefitinib resistance in NSCLC by silencing PDLIM5 using ultrasound-targeted microbubble destruction technology.

Exploring the relationship between autophagy and Gefitinib resistance in NSCLC by silencing PDLIM5 using ultrasound-targeted microbubble destruction technology.
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利用超声靶向微泡破坏技术沉默 PDLIM5 探索 NSCLC 中自噬与吉非替尼耐药之间的关系

DOI:
10.1186/s12935-022-02718-4
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发表时间:
2022-09-25
影响因子:
5.8
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
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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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