مرکز منطقه ای اطلاع رساني علوم و فناوري - SN38-PEG-PLGA-verapamil nanoparticles inhibit proliferation and downregulate drug transporter ABCG2 gene expression in colorectal cancer cells

Author/Authors :

Nagheh, Zahra Department of Biology - Science and Research Branch of Islamic Azad University, Tehran, Iran , Irani, Shiva Department of Biology - Science and Research Branch of Islamic Azad University, Tehran, Iran , Mirfakhraie, Reza Department of Medical Genetics - Shahid Beheshti University of Medical Sciences, Tehran, Iran , Dinarvand, Rassoul Nanotechnology Research Center - Faculty of Pharmacy - Tehran University of Medical Sciences

Abstract :

Nowadays, nanoparticle-based drug delivery systems are recognized to reduce the therapeutic side effects. One of the common problems in cancer treatment is cancer drug resistance, resulting from the over-expression of one energy-dependent transporter that enhances drug efflux. Irinotecan is used for metastatic colorectal cancer. The involvement of ABCG2 transporter in irinotecan resistance has been established. The current study was designed to characterize SN38-loaded pegylated (polyethylene glycol) PLGA [poly(lactic-co-glycolic acid)]-verapamil nanoparticles (NPs), and to distinguish the cytotoxic effect of SN38-PEG-PLGA-Ver NPs and the ability of SN38-PEG-PLGA-Ver NPs to inhibit drug resistance through the inhibition of ABCG2 expression. The surface morphology of nanoparticles was determined by scanning electron microscopy. The drug cytotoxicity of SN38-PEG-PLGA-verapamil nanoparticles was measured by MTT assay with desired concentrations and SN38-PEGPLGA- Ver at different incubation times. Real-time PCR was used to determine the mRNA level of ABCG2, BAX, and BCL2. The cellular uptake assay was performed to show the cellular uptake of nanoparticles. The size of NPs used in this study was about 179 nm with surface charge of -17.1 mV. MTT assay results showed that 1 lmol/L of free drug and 3 lmol/L of NPs could reduce HT29 cells by half (IC50) after 48 and 96 h, respectively. An increase in expression of BAX and a decrease in expression of ABCG2 were observed according to the real-time PCR. No significant change was detected in expression of BCL2. In conclusion, sufficient uptake of SN38-PEG-PLGA-Ver NPs and a significant decrease in expression of ABCG2 and an increase in expression of BAX and BAX/BCL2 ratio was observed after treatment with nanoparticles compared with free SN38. These results reveal that SN38- PEG-PLGA-Ver NPs can be an effective therapeutic method in colon cancer treatments and also may prevent anticancer drug resistance.