Bufalin reverses ABCB1-mediated resistance to docetaxel in breast cancer
Background: Docetaxel (DCT) is widely used in clinical practice, but the drug resistance of breast cancer patients has become an important reason to limit its clinical efficacy. Chan’su is a commonly used traditional Chinese medicine for the treatment of breast cancer. Bufalin (BUF) is a bioactive p...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-03-01
|
| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023010472 |
| _version_ | 1797851934142496768 |
|---|---|
| author | Die Zhang Tingting Jia Xingxing Chen Haopeng Jiang Teng Guo Junjun Dong Hairong Zeng Yixin Wang Yi Yuan |
| author_facet | Die Zhang Tingting Jia Xingxing Chen Haopeng Jiang Teng Guo Junjun Dong Hairong Zeng Yixin Wang Yi Yuan |
| author_sort | Die Zhang |
| collection | DOAJ |
| description | Background: Docetaxel (DCT) is widely used in clinical practice, but the drug resistance of breast cancer patients has become an important reason to limit its clinical efficacy. Chan’su is a commonly used traditional Chinese medicine for the treatment of breast cancer. Bufalin (BUF) is a bioactive polyhydroxy steroid extracted from chan’su and has strong antitumor activity, but there are few studies on reversing drug resistance in breast cancer. The aim of this study is to determine whether BUF can reverse the drug resistance to DCT and restore efficacy in breast cancer. Methodology: The reversal index of BUF was detected by Cell Counting Kit-8 (CCK-8) assays. The effects of BUF on enhancing the apoptosis of DCT were detected by flow cytometry and Western Blot (WB), and the main differential expression levels of sensitive and resistant strains were detected by high-throughput sequencing. Rhodamine 123 assay, WB and ATP Binding Cassette Subfamily B Member 1 (ABCB1) ATPase activity experiments were used to detect the effect of BUF on ABCB1. The nude mouse orthotopic model was constructed to investigate the reversal effect of BUF on DCT resistance in vivo. Results: With BUF intervention, the sensitivity of drug-resistant cell lines to DCT was increased. BUF can inhibit the expression of ABCB1 protein, increase the drug accumulation of DCT in drug-resistant strains, and reduce the ATPase activity of ABCB1. Animal experiments show that BUF can inhibit the growth of drug-resistant tumors in an orthotopic model of breast cancer and decrease the expression of ABCB1. Conclusion: BUF can reverse ABCB1-mediated docetaxel resistance in breast cancer. |
| first_indexed | 2024-04-09T19:25:53Z |
| format | Article |
| id | doaj.art-b4f523d26c7943709945f7266091baeb |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-09T19:25:53Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-b4f523d26c7943709945f7266091baeb2023-04-05T08:17:21ZengElsevierHeliyon2405-84402023-03-0193e13840Bufalin reverses ABCB1-mediated resistance to docetaxel in breast cancerDie Zhang0Tingting Jia1Xingxing Chen2Haopeng Jiang3Teng Guo4Junjun Dong5Hairong Zeng6Yixin Wang7Yi Yuan8Department of Pharmacy, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, ChinaDepartment of Pharmacy, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, ChinaDepartment of Pharmacy, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, ChinaDepartment of Pharmacy, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, ChinaShanghai University of Traditional Chinese Medicine, Shanghai, 200062, ChinaDepartment of Pharmacy, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, ChinaShanghai University of Traditional Chinese Medicine, Shanghai, 200062, China; Corresponding author.Emergency Department, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China; Corresponding author.Department of Pharmacy, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China; Corresponding author.Background: Docetaxel (DCT) is widely used in clinical practice, but the drug resistance of breast cancer patients has become an important reason to limit its clinical efficacy. Chan’su is a commonly used traditional Chinese medicine for the treatment of breast cancer. Bufalin (BUF) is a bioactive polyhydroxy steroid extracted from chan’su and has strong antitumor activity, but there are few studies on reversing drug resistance in breast cancer. The aim of this study is to determine whether BUF can reverse the drug resistance to DCT and restore efficacy in breast cancer. Methodology: The reversal index of BUF was detected by Cell Counting Kit-8 (CCK-8) assays. The effects of BUF on enhancing the apoptosis of DCT were detected by flow cytometry and Western Blot (WB), and the main differential expression levels of sensitive and resistant strains were detected by high-throughput sequencing. Rhodamine 123 assay, WB and ATP Binding Cassette Subfamily B Member 1 (ABCB1) ATPase activity experiments were used to detect the effect of BUF on ABCB1. The nude mouse orthotopic model was constructed to investigate the reversal effect of BUF on DCT resistance in vivo. Results: With BUF intervention, the sensitivity of drug-resistant cell lines to DCT was increased. BUF can inhibit the expression of ABCB1 protein, increase the drug accumulation of DCT in drug-resistant strains, and reduce the ATPase activity of ABCB1. Animal experiments show that BUF can inhibit the growth of drug-resistant tumors in an orthotopic model of breast cancer and decrease the expression of ABCB1. Conclusion: BUF can reverse ABCB1-mediated docetaxel resistance in breast cancer.http://www.sciencedirect.com/science/article/pii/S2405844023010472Breast cancerBufalinDocetaxel resistanceABCB1 |
| spellingShingle | Die Zhang Tingting Jia Xingxing Chen Haopeng Jiang Teng Guo Junjun Dong Hairong Zeng Yixin Wang Yi Yuan Bufalin reverses ABCB1-mediated resistance to docetaxel in breast cancer Heliyon Breast cancer Bufalin Docetaxel resistance ABCB1 |
| title | Bufalin reverses ABCB1-mediated resistance to docetaxel in breast cancer |
| title_full | Bufalin reverses ABCB1-mediated resistance to docetaxel in breast cancer |
| title_fullStr | Bufalin reverses ABCB1-mediated resistance to docetaxel in breast cancer |
| title_full_unstemmed | Bufalin reverses ABCB1-mediated resistance to docetaxel in breast cancer |
| title_short | Bufalin reverses ABCB1-mediated resistance to docetaxel in breast cancer |
| title_sort | bufalin reverses abcb1 mediated resistance to docetaxel in breast cancer |
| topic | Breast cancer Bufalin Docetaxel resistance ABCB1 |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023010472 |
| work_keys_str_mv | AT diezhang bufalinreversesabcb1mediatedresistancetodocetaxelinbreastcancer AT tingtingjia bufalinreversesabcb1mediatedresistancetodocetaxelinbreastcancer AT xingxingchen bufalinreversesabcb1mediatedresistancetodocetaxelinbreastcancer AT haopengjiang bufalinreversesabcb1mediatedresistancetodocetaxelinbreastcancer AT tengguo bufalinreversesabcb1mediatedresistancetodocetaxelinbreastcancer AT junjundong bufalinreversesabcb1mediatedresistancetodocetaxelinbreastcancer AT hairongzeng bufalinreversesabcb1mediatedresistancetodocetaxelinbreastcancer AT yixinwang bufalinreversesabcb1mediatedresistancetodocetaxelinbreastcancer AT yiyuan bufalinreversesabcb1mediatedresistancetodocetaxelinbreastcancer |