Betulinic acid enhanced the chemical sensitivity of esophageal cancer cells to cisplatin by inducing cell pyroptosis and reducing cell stemness

Abstract

Background: Betulinic acid (BA) is a lupine pentacyclic triterpene compound derived from the bark of the white mulberry tree, which has a variety of pharmacological properties. The purpose of this study was to investigate the effects of BA combined with cisplatin on the proliferation, stemness, pyroptosis, and xenograft growth of esophageal carcinoma cells in a nude mouse xenograft model. Methods: The cell survival rate was detected by CCK-8 method. TE-11 cells were treated with 3 μM of BA and 15 μM of cisplatin. The cells were randomly divided into four groups: the control group, the BA group, the cisplatin group, and the BA + Cisplatin group. Western blotting was used to detect the expression levels of Ki67, PCNA, SOX2, OCT4, ASC, and Caspase-1. The xenograft model of nude mice was constructed to detect tumor volume, and the positive expression rates of Ki67 and Caspase-1 were detected by immunohistochemistry. Results: Compared with the control group, Ki67, PCNA, SOX2, and OCT4 levels in the BA and cisplatin groups were significantly lower (P<0.05), while ASC and Caspase-1 levels were significantly higher (P<0.05). Compared with the BA group, Ki67, PCNA, SOX2, and OCT4 levels in the BA + cisplatin group were significantly lower (P<0.05), while ASC and Caspase-1 levels were significantly higher (P<0.05). In the nude mouse xenograft model, compared with the control group, the tumor volume of the BA and cisplatin groups was significantly decreased (P<0.05), the expression rate of Ki67 was significantly decreased (P<0.05), and the expression rate of Caspase-1 was significantly increased (P<0.05). Compared with the BA group, the levels of ASC and Caspase-1 in the BA + cisplatin group were significantly lower (P<0.05), the positive expression rate of Ki67 was significantly lower (P<0.05), and the positive expression rate of Caspase-1 was significantly higher (P<0.05). Conclusions: BA enhances the chemical sensitivity of esophageal cancer cells to cisplatin by inhibiting cell proliferation, reducing cell stemness, and inducing pyroptosis.