Effect of TW37 on the growth of H1975 EGFR‑TKI‑resistant lung cancer cells and its underlying mechanisms

Abstract

Previous studies have suggested that the B‑cell lymphoma 2 (Bcl‑2) inhibitor, TW37, may induce apoptosis of the non‑small cell lung cancer cell line, H1975/epidermal growth factor receptor‑tyrosine kinase inhibitor (EGFR‑TKI), which exhibits secondary resistance to EGFR‑TKI. However, the effects of TW37 on H1975/EGFR‑TKI cells remain unclear. The aim of the present study was to investigate the effects of TW37 on the growth of H1975/EGFR‑TKI cells and explore the underlying mechanisms. An in vitro study was performed, whereby H1975/EGFR‑TKI cells were treated with serially increasing concentrations of TW37. MTT, flow cytometry, migration and transwell invasion assays were preformed to investigate the proliferation, apoptosis, migration and invasion of H1975/EGFR‑TKI cells, respectively. In addition, reverse transcription‑polymerase chain reaction and western blot analyses were performed to detect the mRNA and protein expression levels of apoptosis‑associated factors, respectively. An enzyme‑linked immunosorbent assay was performed to detect phosphatidylinositol [3,4,5] tris‑phosphate (PIP3) expression. The results suggested that the mRNA and protein expression levels of Bcl‑2 were significantly decreased in TW37‑treated cells when compared with the untreated control group. Following treatment with TW37, the proliferation, migration and invasion ability of H1975/EGFR‑TKI cells decreased in a dose‑dependent manner, while the percentage of apoptotic cells increased. In addition, the results demonstrated that TW37 reduced the expression of PIP3 and the phosphorylation of AKT serine/threonine kinase 1 (AKT) in H1975/EGFR‑TKI cells in a dose‑dependent manner. In conclusion, TW37 inhibited H1975/EGFR‑TKI cell growth and induced cell apoptosis potentially via suppression of AKT signaling pathway activation.

Comprehensive review of Bcl‐2 family proteins in cancer apoptosis: Therapeutic strategies and promising updates of natural bioactive compounds and small molecules

“…Furthermore, TW‐37 has exhibited promising synergistic effects when used in combination with other chemotherapeutic agents, such as 5‐fluorouracil and cisplatin, in nasopharyngeal carcinoma (Lu, Li et al, 2017). In lung cancer, TW‐37 has shown potential for overcoming resistance to tyrosine kinase inhibitors such as gefitinib, thereby increasing the sensitivity of lung cancer cells to these therapies (Chen et al, 2018; Liu et al, 2018). However, there are currently preclinical studies on this topic.…”