Improvement of carboplatin chemosensitivity in lung cancer cells by siRNA-mediated downregulation of DLGAP1-AS2 expression
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Sania Ghobadi Alamdari1,2, Reza Mohammadzadeh2, Mohammad Amini1
1Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Abstract:
Despite being one of the primary and most effective treatments for advanced stages of lung cancer, chemotherapy drugs like carboplatin have limitations due to their adverse side effects and the development of drug resistance in lung cancer cells. However, recent studies have shown promising results in using small interfering RNAs (siRNAs) as a therapeutic agent for cancer treatment. Hence, this study aimed to investigate the potential of combining siRNA-DLGAP1-AS2 with carboplatin in human lung cancer cell lines. The viability of the cells was assessed using the MTT assay, and apoptosis induction was examined through Annexin V/Pi staining. Additionally, the effect of the combination on cell cycle arrest and colony formation of lung cancer cells was studied. Furthermore, the expression of Bax, Bcl-2, MMP-2, MMP-9, GCLC, and CD44 was evaluated. Our functional analysis revealed that inhibiting the expression of DLGAP1-AS2 increased the sensitivity of lung cancer cells to carboplatin. Moreover, our study demonstrated that the combination of DLGAP1-AS2 inhibition through siRNA-DLGAP1-AS2 transfection and carboplatin treatment had a tumor-suppressive function, inhibiting the progression and proliferation of A549 lung cancer cells. Therefore, it can be concluded that targeting DLGAP1-AS2 using specific siRNA in combination with carboplatin chemotherapy holds promise as a valuable therapeutic approach for lung cancer.
Insights
Combining DLGAP1-AS2 inhibition with carboplatin chemotherapy enhances lung cancer treatment. This approach overcomes drug resistance and reduces tumor progression in lung cancer cells.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Carboplatin is a key chemotherapy for advanced lung cancer but faces limitations like adverse effects and drug resistance.
- Small interfering RNAs (siRNAs) show therapeutic potential in cancer treatment.
- DLGAP1-AS2 is a potential target in lung cancer therapy.
Purpose of the Study:
- To investigate the combined therapeutic potential of siRNA-DLGAP1-AS2 and carboplatin in human lung cancer cell lines.
- To evaluate the impact of this combination on lung cancer cell viability, apoptosis, cell cycle, and colony formation.
- To analyze the expression of key genes involved in cancer progression and apoptosis.
Main Methods:
- Human lung cancer cell lines were treated with carboplatin and siRNA-DLGAP1-AS2.
- Cell viability was assessed using MTT assays.
- Apoptosis was evaluated via Annexin V/Pi staining.
- Cell cycle arrest, colony formation, and gene expression (Bax, Bcl-2, MMP-2, MMP-9, GCLC, CD44) were analyzed.
Main Results:
- Inhibiting DLGAP1-AS2 expression significantly increased lung cancer cell sensitivity to carboplatin.
- The combination therapy demonstrated a tumor-suppressive effect, inhibiting proliferation and progression in A549 lung cancer cells.
- Modulation of apoptosis-related and metastasis-related gene expression was observed.
Conclusions:
- Targeting DLGAP1-AS2 with siRNA in combination with carboplatin is a promising therapeutic strategy for lung cancer.
- This combination approach may overcome carboplatin resistance and inhibit tumor progression.
- Further research into DLGAP1-AS2 as a therapeutic target for lung cancer is warranted.
