BCR-ABL oncoprotein stimulates cell proliferation and inhibits apoptosis in chronic myeloid leukemia (CML). For cure, imatinib is a widely used tyrosine kinase inhibitor, but developing chemotherapeutic resistance has to be overcome. In this study, we aimed to determine differing genome-wide microRNA (miRNA) and messenger RNA (mRNA) expression profiles in imatinib resistant (K562/IMA-3 μM) and parental cells by targeting STAT5A via small interfering RNA (siRNA) applications. After determining possible therapeutic miRNAs, we aimed to check their effects upon cell viability and proliferation, apoptosis, and find a possible miRNA::mRNA interaction to discover the molecular basis of imatinib resistance. We detected that miR-2278 and miR-1245b-3p were most significantly regulated miRNAs according to miRNome array. Upregulating miR-2278 expression resulted in the inhibition of resistant leukemic cell proliferation and induced apoptosis, whereas miR1245b-3p did not exhibit therapeutic results. Functional analyses indicated that AKT2, STAM2, and STAT5A mRNAs were functional targets for miR-2278 as mimic transfection decreased their expressions both at transcriptional and translational level, thus highlighting miR-2278 as a tumor suppressor. This study provides new insights in discovering the mechanism of imatinib resistance due to upregulating the tumorsuppressor hsa-miR-2278 which stands for a functional therapeutic approach, inhibited leukemic cell proliferation, induced apoptosis, and regain of chemotherapeutic drug response in CML therapy.
The objective of the study was to investigate the cytotoxic and apoptotic effects of Methotrexate (MTX)-loaded chitosan (CS) on LNCaP prostate cancer cell line in vitro. For this purpose, CS nanoparticles (NPs) were synthesized through ionic gelation method and MTX was loaded into the carrier with encapsulation. SEM images of the CS NPs have revealed that they have size of about 85 nm in mono-disperse manner. Drug loading yield was found to be 95.7 % with 470 μg drug/mg NP loading capacity. In vitro drug release study showed that MTX was released in a controlled manner. Cell viability was detected by using trypan blue dye exclusion test and WST-1 cell proliferation assay was performed to show cytotoxic effects of the CS, the MTX and the MTX-loaded NP. IC50 values of CS, MTX and MTX-loaded NPs were assigned from the cell survival plot and were determined as 67.18 μM, 20.21 μM and 2.94 μM at the 72nd hour, respectively. As for apoptosis analysis results, following to MTX-loaded CS treatment of LNCAP cells, apoptotic cell percent was detected as 39.3 % at the 72nd hour, that is, MTX-loaded CS induces 1.85-fold increase in apoptotic cell percent in comparison with that of MTX- induced apoptosis.
Background:
Green synthesis, an alternative method for synthesizing nanoparticles, is cheaper, environmentally friendly, and
does not produce toxic effects. Doxorubicin is a chemotherapeutic agent used in lung cancer. Curcumin is a bioactive compound with
properties such as an anticancer obtained from Curcuma longa.
Objective:
This study’s objective was to develop Doxorubicin and Curcumin loaded magnetic nanoparticles that could be synthesized by
green tea leaves and investigate cytotoxic effects against the A549-luc-C8, non-small cell lung cancer line.
Methods:
Magnetic nanoparticles were synthesized with the green synthesis method. Furthermore, Doxorubicin and Curcumin were
encapsulated into magnetic nanoparticles with the one-pot method and obtained magnetic nanoparticles characterized using FTIR,
SEM/EDX, XRD, and UV-VIS spectrophotometric techniques. After that, The drug release test was performed by dialysis using pH 7.4
phosphate-buffered saline at 37 °C. MTT assay was performed to test the cytotoxicity effect in the A549-luc-C8 cell line.
Results:
FTIR analysis verified the magnetic structure and drug loading. SEM images of magnetic nanoparticle releaved that they had a
size of about 50-60 nm in a mono-disperse manner. Drug release after 24 h was found as 5.8% for doxorubicin and 3.4% for curcumin,
showing controlled release.
Conclusion:
Results showed that the prepared magnetic nanoparticles were thought to had synergistic antitumor activity for A549-lucC8.
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