Durvalumab and taxane family combination therapy enhances the antitumoral effects for NSCLC: An in vitro study

Author:

Firoozi Mohammad‐Reza1ORCID,Sadeghi‐Mohammadi Sanam1,Asadi Milad2,Shekari Najibeh3,Seyed Nejad Farshad4,Alizade‐Harakiyan Mostafa4,Soleimani Zahra1,Zarredar Habib1ORCID

Affiliation:

1. Tuberculosis and Lung Diseases Research Center Tabriz University of Medical Sciences Tabriz Iran

2. Department of Basic Oncology Health Institute of Ege University Izmir Turkey

3. Department of Immunology, School of Medicine Shahid Beheshti University of Medical Sciences Tehran Iran

4. Department of Radiation Oncology, School of Medicine Tabriz University of Medical Sciences Tabriz Iran

Abstract

AbstractImmunotherapy 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 IC50) 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.

Publisher

Wiley

Subject

Cell Biology,Clinical Biochemistry,General Medicine,Biochemistry

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