# Baicalin chemosensitivity enhancement of cisplatin in bladder cancer via autophagy flux inhibition

## TL;DR

Baicalin improves cisplatin effectiveness in bladder cancer by blocking autophagy, a process that helps cancer cells survive.

## Contribution

Baicalin is shown to enhance cisplatin chemosensitivity by inhibiting autophagic flux in bladder cancer cells.

## Key findings

- Baicalin reduced cisplatin's IC50 and inhibited BC cell migration and invasion.
- Baicalin suppressed autophagic flux by reducing lysosomal protein expression and autophagosome-lysosome fusion.
- In vivo experiments showed smaller tumor sizes with baicalin and cisplatin combination.

## Abstract

Cisplatin-based chemotherapy remains the standard treatment for advanced bladder cancer (BC); however, nephrotoxicity and chemoresistance limit its clinical application. Baicalin, a flavonoid metabolite derived from the botanical drug, Scutellaria baicalensis Georgi, has been reported to induces autophagy in BC. However, its regulatory effect on autophagic flux under cisplatin treatment remains unclear.

We used cell counting kit (CCK)-8 and 5-ethynyl-2′-deoxyuridine (EdU) assays to explore the role of baicalin in enhancing the sensitivity of BC cells in vitro. The underlying mechanisms were explored using transmission electron microscopy, western blotting, and immunofluorescence, and these findings were validated in vivo.

CCK-8 and EdU assays indicated that baicalin significantly enhanced the therapeutic effect of cisplatin and reduced its half maximal inhibitory concentration (IC50) value. Baicalin also inhibited the migration and invasion of BC cells. Western blotting indicated that baicalin suppressed cisplatin-induced autophagy by inhibiting autophagic flux, as evidenced by a reduction in the fusion of autophagosomes and lysosomes, along with decreased expression of lysosomal proteins LAMP1, LAMP2, CTSD, and CTSB. The results of the experiment in vivo showed that baicalin enhanced the anti-cancer effect of cisplatin. Tumor size in the combination group was significantly smaller than that in the cisplatin group.

Baicalin enhanced the sensitivity of BC cells to cisplatin by inhibiting autophagic flux through lysosomal activity suppression. This study provides a potential botanical drug candidate for chemosensitization during BC chemotherapy.