Pro-apoptotic effects of metformin and cisplatin in non-small cell Lung Cancer: Modulation of apoptosis-related genes and LncRNAs
Year: 2025
Type: article
Abstract: BACKGROUND: Lung cancer is a leading cause of cancer-related mortality. While cisplatin is a cornerstone of chemotherapy, metformin (Glucophage) has shown anti-cancer potential. This study investigated the effects of cisplatin and metformin (Glucophage) on non-small cell lung cancer (NSCLC) cells, focusing on their combined impact on apoptosis-related genes and lncRNAs. METHODS: The A549 (NSCLC) and MRC5 (normal fibroblast) cell lines were treated with cisplatin, metformin (Glucophage), or a combination thereof. Cell viability was assessed by MTT assay, and apoptosis was quantified by flow cytometry. Expression of Bax, Bcl-2, Caspase 3, PVT1, and MEG3 was analyzed by qRT-PCR. RESULTS: Both cisplatin and metformin (Glucophage) individually reduced A549 cell viability in a dose-dependent manner. Combination Index (CI) analysis revealed an additive interaction (CI = 0.935) between the two agents. This combination was associated with an upregulation of pro-apoptotic Bax and lncRNA MEG3, and a downregulation of anti-apoptotic Bcl-2 and oncogenic lncRNA PVT1. CONCLUSION: The combination of cisplatin and metformin (Glucophage) exerts an additive cytotoxic effect and induces apoptosis in NSCLC cells in vitro. This effect is associated with a favorable modulation of key apoptosis-regulating genes and lncRNAs. These findings provide a strong rationale for further mechanistic and preclinical investigation of this combination therapy for lung cancer.
Authors: Nazanin Sadeghi, Fatemeh Soleimanifar, Elmira Attar, Hamed Haddad Kashani, Romina Ghayoumi, Seyed-Alireza Etesami
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,740
OpenAlex ID: W4417163986