The gelatinases-stimuli nanoparticles reverse docetaxel resistance and epithelial to mesenchymal transition in lung cancer cell line

Background

Drug resistance is a main obstacle for the successful cancer therapy. Emerging evidence suggests that miR-200c functions as an effective cancer stem cells (CSCs) inhibitor and restores sensitivity to microtubule-targeting drugs.

Methods

In the present work, we engineered the intelligent gelatinases-stimuli nanoparticles (NPs) to co-delivery miR-200c and antitumor drug docetaxel (DOC) to verify their synergetic effects on inhibition of CSCs and cancer cells. After tumor cells were treated with miR-200c NPs, miR-200c and its targeted gene class III beta-tubulin (TUBB3) expression were evaluated. The effects of (miR-200c + DOC) NPs on DOC-resistant lung cancer cells viability as well as the expression of E-cadherin and CD44 were studied.

Results

We found that the (miR-200c + DOC) NPs significantly overcome DOC resistance, possibly by elevated miR-200c expression,low TUBB3 level, and reversed the EMT through upregulation E-cadherin and inhibition lung CSCs.

Conclusions

The (miR-200c + DOC) NPs may provide a new modality for co-delivery of nucleic acid and drugs to inhibit CSCs and reverse drug resistance.

Clinical trial identification

Legal entity responsible for the study

Qin Liu

Funding

The National Nature Science Foundation of China (81302053)

Disclosure

All authors have declared no conflicts of interest.