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Published on: September 18, 2018
Chitosan/pshRNA plasmid nanoparticles targeting MDR1 gene reverse paclitaxel resistance in ovarian cancer cells
Yan Yang1, Zehua Wang, Minfang Li
1Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. lindayanyang@126.com
Abstract:
In order to investigate the effect of chitosan/pshRNA plasmid nanoparticles targeting MDR1 genes on the resistance of A2780/TS cells to paclitaxel, chitosan/pshRNA plasmid nanoparticles were synthesized by means of a complex coacervation technique and transfected into A2780/TS cells. The cells transfected with MDR1-targeted chitosan/pshRNA plasmid nanoparticles were experimental cells and the cells transfected with chitosan/pGPU6/GFP/Neo no-load plasmid nanoparticles served as negative control cells. Morphological features of the nanoparticles were observed under transmission electron microscope (TEM). MDR1 mRNA expression was assessed by RT-PCR. Half-inhibitory concentration (IC50) of paclitaxel for A2780/TS cells was determined by MTT method. TEM showed that the nanoparticles were round-shaped, smooth in surface and the diameters varied from 80 to 120 nm. The MDR1 mRNA in the transfected cells was significantly decreased by 17.6%, 27.8% and 52.6% on the post-transfection day 2, 4 and 7 when compared with that in A2780/TS cells control (P<0.05). MTT assay revealed that the relative reversal efficiency was increased over time and was 29.6%, 51.2% and 61.3% respectively in the transfected cells 2, 4, 7 days after transfection and IC50 (0.197+/-0.003, 0.144+/-0.001, 0.120+/-0.004) were decreased with difference being significant when compared with that in A2780/TS (0.269+/-0.003) cells control (P<0.05). It was concluded that chitosan/pshRNA plasmid nanoparticles targeting MDR1 can effectively reverse the paclitaxel resistance in A2780/TS cells in a time-dependent manner.
Insights
Chitosan/pshRNA plasmid nanoparticles targeting MDR1 genes effectively reversed paclitaxel resistance in A2780/TS cells. This drug resistance reversal was observed in a time-dependent manner, showing significant improvements over seven days.
Area of Science:
- Biotechnology
- Nanomedicine
- Cancer Research
Background:
- Paclitaxel resistance in A2780/TS cells poses a significant challenge in ovarian cancer treatment.
- Multidrug resistance (MDR1) gene expression is a key mechanism contributing to paclitaxel resistance.
Purpose of the Study:
- To investigate the efficacy of chitosan/pshRNA plasmid nanoparticles targeting MDR1 genes in overcoming paclitaxel resistance in A2780/TS cells.
- To evaluate the time-dependent effects of these nanoparticles on MDR1 gene expression and drug sensitivity.
Main Methods:
- Chitosan/pshRNA plasmid nanoparticles were synthesized using complex coacervation and transfected into A2780/TS cells.
- Nanoparticle morphology was assessed via transmission electron microscopy (TEM).
- MDR1 mRNA expression was quantified using RT-PCR, and paclitaxel sensitivity was determined by MTT assay.
Main Results:
- TEM confirmed round-shaped nanoparticles (80-120 nm).
- Significant reduction in MDR1 mRNA expression (up to 52.6%) was observed by day 7 post-transfection.
- Relative reversal efficiency of paclitaxel resistance increased over time, reaching 61.3% by day 7, with a corresponding decrease in IC50 values.
Conclusions:
- Chitosan/pshRNA plasmid nanoparticles targeting MDR1 effectively reverse paclitaxel resistance in A2780/TS cells.
- The observed reversal of drug resistance is time-dependent, highlighting the potential of this nanocarrier system for overcoming chemotherapy resistance.
