(69b) Co-Administration of the Tumor-Penetrating Peptide Irgd Improves the Therapeutic Efficacy of paclitaxel in a 3D Air-Grown Lung Cancer Model

Current cancer research relies on two-dimensional (2D) cell culture, which does not recapitulate in vivo conditions in their entirety. Due to this unnatural microenvironment, 2D cell assays often provide unpredictable and contrasting results in comparison to animal studies and clinical trials, and contributes to the low success rates and high costs associated with drug development. Three-dimensional (3D) spheroids are better representative of cancer cells that tend to form solid tumors in vivo. By exhibiting intrinsic physiological and morphological characteristics similar to tumor tissue, 3D spheroids closely mimic in vivo biology and are characterized for having hypoxic cells and a necrotic core, which often gives them high resistance to the treatments.

3D cell culture platforms are increasingly being used in cancer research and drug development since they mimic avascular tumors in vitro. In the present study, we focused on the development of air-grown multicellular spheroids (MCS) to mimic in vivo tumors for understanding lung cancer biology and improving treatment methods. 3D MCS were formed using A549 lung adenocarcinoma cells, comprising cellular heterogeneity with different proliferative and metabolic gradients. The growth kinetics, morphology, and 3D structure of the MCS were characterized by brightfield, fluorescent, and scanning electron microscopy. In a drug resistance study MCS demonstrated significant decrease in the growth when the tumor penetrating peptide iRGD and paclitaxel (PTX) were co-administered as compared to PTX alone. It was also found that when treated with both iRGD and PTX, A549 MCS exhibited an increase in apoptosis and decrease in clonogenic survival capacity as compared to PTX treatment alone. This study demonstrated that co-administration of iRGD resulted in the improvement of tumor penetration ability of PTX in an in vitro A549 3D MCS model. In addition, this is the first time an air-grown lung cancer tumor spheroid model has been developed and evaluated.

Keywords: Lung cancer; Spheroids; Tumor-penetrating peptide iRGD; Paclitaxel, A549 lung adenocarcinoma