Durvalumab and taxane family combination therapy enhances the antitumoral effects for NSCLC: An in vitro study.
Mohammad-Reza FirooziSanam Sadeghi-MohammadiMilad AsadiNajibeh ShekariFarshad Seyed NejadMostafa Alizade-HarakiyanZahra SoleimaniHabib ZarredarPublished in: Cell biochemistry and function (2024)
Immunotherapy has lately become the most preferred cancer treatment method, and for non-small cell lung cancer (NSCLC) first-line treatment, there are many immunotherapy options. This study aimed to assess the effectiveness and toxicity of paclitaxel (PTX), docetaxel (DTX) chemotherapy, immune checkpoint inhibitor treatment (durvalumab; DVL), and their combination in NSCLC. A-549 cells were treated with DVL in combination with PTX and DTX (a quarter of the IC 50 ) to investigate their anticancer effects on these cells. The MTT assay, wound healing tests, and double-staining with Annexin V/PI were used to assess the cell viability, apoptosis, and migration. The results showed that a combination of 0.35 mg/mL DVL with 6.5 μg/mL PTX and 1.75 μg/mL DTX produced a synergistic effect with CI values of 0.88, 0.37, and 0.81, respectively. Moreover, the PTX + DTX + DVL combination led to a significantly increased apoptotic rate up to 88.70 ± 3.39% in the A549 cell line compared to monotherapy (p < .001). In addition, we found that the combination therapy with these agents increased the expression level of Bax, Cas-3, p53, and Bax/Bcl-2 ratio in all experimental groups. In conclusion, the results suggest that combining anti-PD-L1 antibody therapy with chemotherapy may provide a promising approach to enhance treatment outcomes and be a potentially efficacious strategy for treating NSCLC patients. Further research and clinical investigations are needed to elucidate the underlying molecular mechanisms and validate the therapeutic potential of these compounds in vivo.
Keyphrases
- combination therapy
- induced apoptosis
- small cell lung cancer
- cell cycle arrest
- endoplasmic reticulum stress
- oxidative stress
- cell death
- advanced non small cell lung cancer
- signaling pathway
- end stage renal disease
- locally advanced
- newly diagnosed
- ejection fraction
- brain metastases
- crispr cas
- wound healing
- randomized controlled trial
- poor prognosis
- chronic kidney disease
- pi k akt
- genome editing
- squamous cell carcinoma
- mesenchymal stem cells
- cell proliferation
- radiation therapy
- long non coding rna
- single cell
- bone marrow
- anti inflammatory
- open label
- cell therapy
- tyrosine kinase
- smoking cessation