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Published on: February 9, 2024
Sensitization of Resistance Ovarian Cancer Cells to Cisplatin by Biogenic Synthesized Silver Nanoparticles through
Tayebe Ramezani1, Mohamad Nabiuni1, Javad Baharara2
1Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
Abstract:
Today, drug resistance is one of the major problems in fight against cancer. Therefore, combination of therapeutic strategies was raised to effectively improve disease prognosis. In this regard, silver nanoparticles (AgNPs) are considered significant due to their anticancer properties. This study aimed to return sensitivity to cisplatin to A2780 cisplatin-resistance cell lines in the presence of biogenic synthesis curcumin-coated silver nanoparticles (cAgNPs). Synergic cellular effects of cAgNPs and cisplatin on ovarian carcinoma 2780 resistant to cisplatin cells were assessed using MTT assay, Acridine orange (AO)/propidium iodide (PI), DAPI staining, Annexin V/PI assay, and caspase 3/9 activation assay. Finally, expression of p53 and MMP-9 genes were evaluated using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). According to the results, 8 µg/mL and 62 µg/mL of cAgNPs and cisplatin led to 50% cell death in 48 h, respectively. Therefore, we combined non-toxic concentration of nanoparticles (1-5 µg/mL) with cisplatin (2.5 µg/mL). Decreased proliferation rate was about 50% for synergic use of cisplatin (2.5 µg/mL) and cAgNPs (2 µg/mL). According to the results, cell death induction significantly increased by AO/PI, DAPI staining and Annexin V/PI assay in the combined group. Moreover, activity of caspase 3/9 significantly increased in the mentioned group. The combined use of cAgNPs and cisplatin resulted in upregulated expression of p53 gene and downregulated expression of MPP-9 gene. As observed in this study, a combination of cAgNPs and cisplatin increased the efficiency of apoptosis induction in A2780 cells, compared to the independent use of cisplatin or cAgNPs.
Insights
Curcumin-coated silver nanoparticles (cAgNPs) combined with cisplatin restore sensitivity in drug-resistant ovarian cancer cells. This synergistic approach enhances apoptosis and upregulates p53, offering a promising strategy against cisplatin resistance.
Area of Science:
- Nanomedicine
- Cancer Therapeutics
- Drug Resistance
Background:
- Drug resistance is a major challenge in cancer treatment, necessitating novel therapeutic strategies.
- Silver nanoparticles (AgNPs) exhibit anticancer properties and are explored for combination therapies.
- Curcumin-coated silver nanoparticles (cAgNPs) offer potential synergistic effects with conventional chemotherapeutics.
Purpose of the Study:
- To investigate the synergistic effects of biogenic curcumin-coated silver nanoparticles (cAgNPs) and cisplatin on cisplatin-resistant ovarian cancer cells (A2780).
- To evaluate the ability of cAgNPs to restore sensitivity to cisplatin in resistant ovarian cancer models.
- To assess the impact of combined therapy on apoptosis induction and gene expression.
Main Methods:
- Cell viability was assessed using MTT assay.
- Apoptosis was evaluated through Acridine orange/propidium iodide (AO/PI), DAPI staining, and Annexin V/PI assays.
- Caspase 3/9 activation and gene expression (p53, MMP-9) via RT-PCR were analyzed.
Main Results:
- Combined treatment with non-toxic concentrations of cAgNPs (2 µg/mL) and cisplatin (2.5 µg/mL) reduced proliferation by approximately 50%.
- Synergistic use significantly increased apoptosis induction, as evidenced by AO/PI, DAPI, and Annexin V/PI assays.
- Combined therapy led to increased caspase 3/9 activity, upregulated p53 expression, and downregulated MMP-9 expression.
Conclusions:
- Combination of cAgNPs and cisplatin effectively overcomes cisplatin resistance in ovarian cancer cells.
- The synergistic approach enhances apoptosis through caspase activation and modulation of p53 and MMP-9.
- This combination therapy presents a promising strategy to improve treatment outcomes for cisplatin-resistant ovarian cancer.
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