Bufotaline Enhances the Sensitivity of Pancreatic Cancer Cells to Adriamycin Treatment by Inhibiting DNA Damage Repair
10.13865/j.cnki.cjbmb.2025.06.1244
- VernacularTitle:蟾毒它灵通过抑制DNA损伤修复增加胰腺癌细胞对阿霉素化疗敏感性
- Author:
Ming-Wen YIN
1
;
Shu-Ting HAN
1
;
Jiao XUE
1
;
Jun-Jie MIAO
1
;
Shi-Ying ZHAO
1
;
Ze YU
1
;
Jing JIN
1
Author Information
1. 包头医学院生物化学与分子生物学教研室,内蒙古包头 014040
- Publication Type:Journal Article
- Keywords:
pancreatic cancer(PCA);
DNA damage response;
Bufotaline;
chemotherapy sensitivity
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(10):1410-1420
- CountryChina
- Language:Chinese
-
Abstract:
Pancreatic cancer has emerged as one of the most challenging malignancies worldwide,with its high resistance to chemotherapy being the primary cause of treatment failure.Therefore,enhancing the chemosensitivity of pancreatic cancer has become a major focus of current research.In this study,we in-vestigated how Bufotaline,a bufadienolide extracted from the traditional Chinese medicine toad venom,exhibits its antitumor activity.Specifically,we explored the potential of Bufotaline to enhance the chemo-sensitivity of pancreatic cancer cells to Adriamycin and elucidated its underlying molecular mechanisms.Using CCK-8 and colony formation assays,we demonstrated that Bufotaline enhances the inhibitory effect of Adriamycin on the survival of pancreatic cancer cell lines Patu-8988T,Aspc-1,and Patu-8988S.No-tably,Bufotaline treatment reduced the IC50 of Adriamycin in drug-resistant pancreatic cancer cells to lev-els comparable to those in non-resistant cells.Results from Western blot,immunofluorescence,comet as-say,and TUNEL assays revealed that Bufotaline promotes Adriamycin-induced DNA damage in pancreatic cancer cells.RNA-seq analysis of Patu-8988T cells treated with Adriamycin alone or in combination with Bufotaline showed significant changes in gene expression,and qRT-PCR analysis further confirmed that Bu-fotaline downregulates the expression of DNA damage repair proteins NBS1 and RAD50.Moreover,Western blot analysis revealed that Bufotaline reduces the levels of DNA damage response repair proteins,and Im-munofluorescence experiments indicated that Bufotaline inhibits the activation of the ATM/CHK2 signaling pathway.Finally,in a subcutaneous xenograft mouse model,the combination of Adriamycin and Bufotaline treatment significantly suppressed pancreatic cancer cell growth.In conclusion,Bufotaline enhances Adria-mycin-induced chemosensitivity in pancreatic cancer cells;the combination of Adriamycin and Bufotaline downregulates the expression of DNA damage response repair proteins NBS1 and RAD50,and inhibits the ATM/CHK2-mediated DDR signaling pathway,thereby delaying DNA damage repair.
