BUB1B promotes gemcitabine resistance in lung adenocarcinoma and activates the PI3K/AKT signaling pathway.

Abstract

Purpose: Lung adenocarcinoma (LUAD) exhibits aggressive biological behavior and a poor prognosis. Gemcitabine is the first-line chemotherapy drug for advanced LUAD but has a low response rate. This study aims to explore the effect of BUB1B on gemcitabine resistance in LUAD.

Methods: The data in the cancer genome atlas (TCGA) database was analyzed to clarify the expression of BUB1B in lung cancer and its relationship with clinical features. LUAD samples were collected to confirm BUB1B expression in lung cancer by qRT-PCR and Western Blot. The effects of gemcitabine on cell proliferation, apoptosis, and invasiveness were explored by overexpressing and silencing BUB1B in vitro and in vivo. Changes in PI3K/AKT were detected by Western Blot.

Results: BUB1B had higher expression in tumor tissues than in normal tissues and was associated with a worse prognosis (P < 0.05). The GSEA results showed that the G2m checkpoint and the PI3K / AKT pathway were differentially enriched in the LUAD samples. Inhibition of BUB1B expression affected proliferation activity, clone formation ability, and invasion ability of tumor cells. Meanwhile, inhibition of BUB1B expression increased tumor cell apoptosis rate and increased lung cancer cell sensitivity to gemcitabine among inhibition of the PI3K / AKT pathway. Furthermore, inhibition of BUB1B expression increased the sensitivity of lung cancer cells to gemcitabine, which was further validated in vivo.

Conclusions: BUB1B may be a potentially useful prognostic molecular biomarker associated with poor survival in patients with LUAD and could regulate the sensitivity of lung cancer cells to gemcitabine and activates the PI3K/AKT pathway.