Heparin-binding epidermal growth factor inhibits apoptosis in cisplatin-resistant pancreatic cancer cells via upregulation of EGFR and ERCC 1 expressions

Abstract

Purpose: To investigate the influence of heparin-binding epidermal growth factor (HB-EGF) on apoptosis in cisplatin-resistant pancreatic cancer cells, as well as its mechanism of action. Methods: Pancreatic cancer cisplatin-resistant cells (BXPC-3/CDDP) were transfected with HB-EGF small interfering RNA (siRNA). The cells were randomly assigned to four groups, namely, BXPC-3 group (group A), BXPC-3/CDDP group (group B), transfected group A (group Asi) and transfected group B (group Bsi). Cell proliferation was determined using MTT assay, and the levels of expression of HBEGF, epidermal growth factor receptor (EGFR) and excision repair cross-complementation group 1 (ERCC 1) were determined using Western blotting. The extent of apoptosis was determined by flow cytometry. Results: Cell proliferation was increased in group B, relative to group A, but was significantly decreased after transfection with HB-EGF siRNA (p < 0.05). The half-maximal inhibitory concentration (IC50) of group Bsi was reduced, relative to group Asi (p < 0.05). The expression of HB-EGF was significantly upregulated in group B, relative to group A (p < 0.05). In contrast, HB-EGF siRNA transfection of the cells significantly down-regulated HB-EGF expression (p < 0.05). Early apoptosis was significantly higher in group A than in groups B and Bsi. Higher levels of apoptosis were seen in group Bsi, relative to group B after inhibition of HB-EGF expression (p < 0.05). Conclusion: These results indicate that HB-EGF is resistant to cisplatin, and it inhibits apoptosis in pancreatic cancer cells via the upregulation of EGFR and ERCC 1 expressions.