ANTICANCER EFFECTS OF EMETINE AGAINST CISPLATIN-RESISTANT PANCREATIC CANCER CELLS VIA ACTIVATION OF CYTO-C/CASPASE-9/CASPASE-3/BAX/BAD AXIS.

TING YIN; ZHAO YIN; HUI YANG

This investigation examined the potential pharmacotherapeutic efficacy of emetine, a natural alkaloid, against pancreatic ductal carcinoma, utilizing the PaCa3 cell line as a model. Employing a multifaceted approach, the study explored emetine's impact on cell viability, clonogenic potential, and apoptotic pathways, unravelling its molecular mechanisms. Additionally, an in vivo assessment was conducted to evaluate emetine's antitumor efficacy against PaCa3 xenografts. Under standard conditions, PaCa3 cells were treated with varying emetine concentrations and subjected to MTT, clonogenic, DAPI, AO/EB, Annexin V-FITC/PI, and Western blot assays. In vivo experiments involved the administration of emetine to female nude mice with PaCa3 xenografts, with subsequent measurement of tumor weight and volume. Statistical analyses included Tukey-test and ANOVA. Emetine demonstrated a significant and doseand time-dependent cytotoxic effect on PaCa3 cells, reducing viability from 98% to 8% (***p < 0.001). Clonogenic assay indicated a substantial inhibition of colony formation. DAPI staining revealed nuclear chromatin condensation, while AO/EB staining indicated heightened apoptosis. Annexin V-FITC/PI assay exhibited a dose-dependent decrease in normal cell viability and an increase in apoptotic events. Western blot analysis showed a concentration-dependent downregulation of anti-apoptotic Bcl-2 and the upregulation of pro-apoptotic markers. In vivo experiments illustrated a dose-dependent reduction in tumor weight (5 g to 1.6 g) and volume (2400 mm³ to 844 mm³) with emetine treatment. In conclusion, emetine emerges as a potent anticancer agent against pancreatic ductal carcinoma, exhibiting cytotoxicity, clonogenic inhibition, and apoptotic induction in PaCa3 cells. The in vivo study further highlights its promising therapeutic potential, laying the groundwork for future clinical studies in pancreatic cancer treatment.

PANCREATIC duct; DUCTAL carcinoma; WESTERN immunoblotting; APOPTOSIS inhibition; CYTOTOXINS

Acta Poloniae Pharmaceutica, 2024, Vol 81, Issue 3, p373

0001-6837

Academic Journal

10.32383/appdr/190457