Induction of Apoptosis in TKI-Resistant Non-Small Cell Lung Cancer: Evaluating the Effects of AB680

Abstract

The most commonly diagnosed cancer worldwide is lung cancer. EGFR-mutated lung cancer is usually treated with tyrosine kinase inhibitors (TKIs) including erlotinib. However, drug resistance toward TKI eventually developed. Therefore, investigating an alternative therapeutic method to combat this resistance is important. TKI resistance is mostly due to adenosine, which is produced by CD73 resulting in immune evasion and proliferation. One approach that is viable is through the inhibition of CD73 which can decrease the adenosine level in the cells and lead the cell to undergo apoptosis (cell death) or directly lead the cells to apoptosis. This study employs cell viability and western blot analysis in order to assess whether AB680 can decrease cell viability while increasing the expression of apoptosis markers through western blot. Our study found that erlotinib-resistant PC9 (PC9ER) cells are more tolerant to AB680 compared to PC9 cells which is observed through the viability of the cells after being treated with different concentrations of AB680. The noticeable difference in cell viability is exhibited by PC9 cells that are treated with 0.8μM and 0.6μM AB680. Upon this finding, both PC9 and PC9ER cells were treated with 0.8μM and 0.6μM AB680 for 48 and 72 hours in order to observe the cell's apoptosis marker. It is found that both PC9 and PC9ER cells treated with 0.8μM and 0.6μM AB680 for 48 and 72 hours do not exhibit increased expression of apoptosis markers. These phenomena suggest other mechanisms may play a role.