Abstract:

Berberine, a natural isoquinoline alkaloid, has demonstrated anticancer properties in various malignancies. This systematic review and meta-analysis evaluated the efficacy of berberine specifically in lung cancer preclinical models. We conducted a comprehensive literature search across PubMed, Web of Science, and Scopus. From 427 initially identified publications, three high-quality preclinical studies met inclusion criteria, providing data on 172 experimental animals for tumor volume analysis and 134 animals for tumor weight assessment. Berberine significantly inhibited tumor volume (SMD -1.5140, 95% CI: -2.0164 to - 1.0116; p<0.0001) and tumor weight (SMD -2.0546, 95% CI: -2.5484 to -1.5607; p<0.0001) in experimental lung cancer models. Considerable heterogeneity was observed across studies (I²=92.1% for tumor volume, I²=87.6% for tumor weight). Mechanistically, berberine exhibited p53-dependent antitumor activity, demonstrated oral bioavailability through dietary administration, and functioned as a small-molecule immune checkpoint inhibitor by reducing PD-L1 expression on tumor cells.Berberine demonstrates significant antitumor activity in lung cancer models through multiple complementary mechanisms. Despite the robust preclinical evidence, the limited number of included studies necessitates further investigation through standardized protocols and carefully designed clinical trials to evaluate berberine's potential as an adjunctive or alternative therapy for lung cancer.

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