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Pleiotrophin affects the susceptibility of prostate cancer cells to cisplatin
Qiuru Che1, Liwei You, Yumeng Dai
1The Center for Combinatorial Chemistry and Drug Discovery, the School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin, People's Republic of China.
Abstract:
Drug resistance is a major problem in cancer therapy with cisplatin. It has not been reported that pleiotrophin, which is anti-apoptotic in some cancer cells, is associated with cisplatin resistance. Pleiotrophin was exogenously expressed in 293 cells. Viability and apoptosis of PC3 cells treated with different concentrations of cisplatin in the presence or absence of purified pleiotrophin were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. PC3 cells transfected with shRNAs were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting 24 h after transfection. MTT assay data indicated that the EC50 value of cisplatin for PC3 cells was significantly increased in the presence of pleiotrophin. Flow cytometry data demonstrated the pleiotrophin dose-dependent anti-apoptosis in PC3 cells treated with cisplatin. Knockdown of pleiotrophin with sh-RNA, as justified by RT-PCR and western blotting analysis, led to increased cisplatin induced-apoptosis in PC3 cells with an increased level of the cleaved poly ADP-ribose polymerase protein. Pleiotrophin may be a potential antiapoptotic protein associated with cisplatin susceptibility, which warrants further study on the role of pleiotrophin in cisplatin resistance.
Insights
Pleiotrophin, an anti-apoptotic protein, may contribute to cisplatin resistance in cancer therapy. Reducing pleiotrophin levels increases cisplatin-induced apoptosis, suggesting its role in overcoming drug resistance.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Cisplatin resistance is a significant challenge in cancer treatment.
- The role of pleiotrophin (PTN) in cisplatin resistance remains largely uncharacterized.
- PTN exhibits anti-apoptotic properties in certain cancer cell types.
Purpose of the Study:
- To investigate the association between pleiotrophin and cisplatin resistance in PC3 cancer cells.
- To determine if pleiotrophin influences cisplatin-induced apoptosis.
- To explore the potential of targeting pleiotrophin to enhance cisplatin efficacy.
Main Methods:
- Exogenous expression of pleiotrophin in 293 cells.
- MTT assay to assess cell viability and cisplatin EC50 values.
- Flow cytometry to quantify apoptosis.
- RT-PCR and Western blotting to analyze pleiotrophin knockdown via shRNA.
Main Results:
- Pleiotrophin significantly increased the EC50 value of cisplatin in PC3 cells, indicating reduced sensitivity.
- Pleiotrophin demonstrated a dose-dependent anti-apoptotic effect in PC3 cells treated with cisplatin.
- Knockdown of pleiotrophin using shRNA enhanced cisplatin-induced apoptosis and increased cleaved PARP levels.
Conclusions:
- Pleiotrophin acts as an anti-apoptotic protein that may confer resistance to cisplatin.
- Targeting pleiotrophin could be a potential strategy to overcome cisplatin resistance in cancer therapy.
- Further research is warranted to elucidate the precise mechanisms of pleiotrophin in cisplatin resistance.
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