| Title |
Combination Therapy with AKT3 and PI3KCA siRNA Enhances the Antitumor Effect of Temozolomide and Carmustine in T98G Glioblastoma Multiforme Cells
|
|---|---|
| Published in |
BioDrugs, February 2016
|
| DOI | 10.1007/s40259-016-0160-y |
| Pubmed ID | |
| Authors |
Monika Paul-Samojedny, Adam Pudełko, Małgorzata Kowalczyk, Anna Fila-Daniłow, Renata Suchanek-Raif, Paulina Borkowska, Jan Kowalski |
| Abstract |
Glioblastoma multiforme (GBM) is the most malignant and invasive human brain tumor, and it is characterized by a poor prognosis and short survival time. Current treatment strategies for GBM, using surgery, chemotherapy and/or radiotherapy, are ineffective. The PI3K/AKT/PTEN signaling pathway is frequently deregulated in this cancer, and it is connected with regulation of the cell cycle, apoptosis, and autophagy. The current study was undertaken to examine the effect of small interfering RNA (siRNA) targeting the AKT3 and PIK3CA genes on the susceptibility of T98G cells to temozolomide (TMZ) and carmustine (BCNU). T98G cells were transfected with AKT3 or PI3KCA siRNA. Transfection efficiency was assessed using flow cytometry and fluorescence microscopy. The influence of AKT3 and PI3KCA siRNA in combination with TMZ and BCNU on T98G cell viability, proliferation, apoptosis, and autophagy was evaluated as well. Alterations in messenger RNA (mRNA) expression of apoptosis-related and autophagy-related genes were analyzed using quantitative reverse transcription polymerase chain reaction (QRT-PCR). Transfection of T98G cells with AKT3 or PI3KCA siRNA and exposure to TMZ and BCNU led to a significant reduction in cell viability, accumulation of subG1-phase cells, and reduction of cells in the S and G2/M phases, as well as induction of apoptosis or necrosis, and regulation of autophagy. The siRNA-induced AKT3 and PI3KCA mRNA knockdown in combination with TMZ and BCNU inhibited proliferation and induced apoptosis and autophagy in T98G cells. Thus, knockdown of these genes in combination with TMZ and BCNU may offer a novel therapeutic strategy to more effectively control the growth of human GBM cells, but further studies are necessary to confirm a positive phenomenon for the treatment of GBM. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Brazil | 1 | 3% |
| Unknown | 31 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 5 | 16% |
| Student > Bachelor | 5 | 16% |
| Student > Master | 5 | 16% |
| Student > Ph. D. Student | 4 | 13% |
| Student > Doctoral Student | 2 | 6% |
| Other | 5 | 16% |
| Unknown | 6 | 19% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 9 | 28% |
| Biochemistry, Genetics and Molecular Biology | 5 | 16% |
| Agricultural and Biological Sciences | 4 | 13% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 6% |
| Engineering | 2 | 6% |
| Other | 0 | 0% |
| Unknown | 10 | 31% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 February 2016.
All research outputs
#20,310,658
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Outputs from BioDrugs
#634
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Outputs of similar age from BioDrugs
#6
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