Chitosan/pshRNA plasmid nanoparticles targeting MDR1 gene reverse paclitaxel resistance in ovarian cancer cells
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Synthesis and Characterization of Placental Chondroitin Sulfate A (plCSA)-Targeting Lipid-Polymer Nanoparticles
Published on: September 18, 2018
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.
