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Background: Non-small cell lung cancer (NSCLC), the most prevalent lung cancer subtype, presents significant treatment challenges. Cisplatin (CP) -based regimens are central to the treatment of multiple solid tumors, but its use is restricted due to its dose-related renal toxicity. We previously found that fluorofenidone 1-3-fluorophenyl-5-methyl-2- (1H) -pyridone (AKF-PD) effectively reverses CP-induced acute kidney injury (AKI). However, it remains unclear whether AKF-PD can synergistically ameliorate NSCLC when used together with CP. Thus, this study sought to investigate the effect of AKF-PD on NSCLC and examined its combinatory use with CP for cancer treatment. Methods: We conducted cell viability assays, 5-ethynyl-2'-deoxyuridine (EdU) experiments, colony-forming assays, wound-healing tests, and Transwell experiments in A549 and H1299 cells to explore the effects of AKF-PD on NSCLC. We then detected the epithelial-mesenchymal transition (EMT) markers i. e. , epithelial cadherin (E-cadherin), matrix metallopeptidase 9 (MMP9), vimentin, and snail family transcriptional repressor 1 (SNAIL), phosphoinositide 3-kinase (PI3K) /protein kinase B (AKT) /mechanistic target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK), to identify the potential mechanisms of AKF-PD. Further, via the combined use of AKF-PD and CP, we found that AKF-PD enhanced the antitumor effect of CP, and we suggest that this may be due to its inhibitory effect on EMT. We also examined the effect of combining AKF-PD and CP in other cancer cell lines, including Hela, SiHA, MDA-MB-231, 5-8F, and UM-UC-3 cells. Results: AKF-PD significantly inhibited the proliferation and invasion of NSCLC cells (A549 and H1299), suppressed the activation of the MAPK and PI3K/AKT/mTOR pathways, and inhibited the EMT of the tumor cells. When AKF-PD was used in combination with CP, these effects were further enhanced. We also found that AKF-PD enhanced the anti-cancer effect of CP in a variety of cancer cell lines, including cervical cancer (Hela cells and SiHA cells), nasopharyngeal cancer (5-8F cells), triple-negative breast cancer (MDA-MB-231 cells), and bladder cancer (UM-UC-3 cells). Conclusions: AKF-PD not only mitigates CP-induced AKI but also enhances the anti-cancer efficacy of CP. Our findings provide valuable insights into the treatment of NSCLC and may have clinical applications.
Wang et al. (Fri,) studied this question.