Ginsenoside panaxatriol reverses TNBC paclitaxel resistance by inhibiting the IRAK1/NF-κB and ERK pathways
Background Paclitaxel (PTX) resistance is a major obstacle in the treatment of triple-negative breast cancer (TNBC). Previously, we have reported that interleukin-1 receptor-associated kinase 1 (IRAK1) and its downstream pathways are associated with PTX resistance in TNBC cells. In this study, we so...
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PeerJ Inc.
2020-06-01
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| Online Access: | https://peerj.com/articles/9281.pdf |
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| author | Panpan Wang Dan Song Danhong Wan Lingyu Li Wenhui Mei Xiaoyun Li Li Han Xiaofeng Zhu Li Yang Yu Cai Ronghua Zhang |
| author_facet | Panpan Wang Dan Song Danhong Wan Lingyu Li Wenhui Mei Xiaoyun Li Li Han Xiaofeng Zhu Li Yang Yu Cai Ronghua Zhang |
| author_sort | Panpan Wang |
| collection | DOAJ |
| description | Background Paclitaxel (PTX) resistance is a major obstacle in the treatment of triple-negative breast cancer (TNBC). Previously, we have reported that interleukin-1 receptor-associated kinase 1 (IRAK1) and its downstream pathways are associated with PTX resistance in TNBC cells. In this study, we sought to investigate the combination treatment of ginsenoside panaxatriol (GPT), one of the main active components in Panax ginseng, with PTX on viability and apoptosis of TNBC PTX resistant cells, and explore the role of IRAK1 mediated signaling pathways in the therapeutic effects. Methods CellTiter-Glo and colony formation assays were used to assess cell viability. Flow cytometry was used to analyze subG1 and apoptosis. Western blot was used to detect expressions of proteins involved in apoptosis and the IRAK1/NF-κB and ERK pathways. The mRNA expression of inflammatory cytokines, S100A7/8/9 and cancer stem cell (CSC)-related genes were examined by qPCR. Stem cells were identified by tumor sphere assay. Cell invasion ability was examined by transwell assay. Results We show that GPT inhibits MDA-MB-231 PTX resistant (MB231-PR) cell viability in a dose-dependent manner. When combined with PTX, GPT synergistically causes more cell death, induces subG1 accumulation and cell apoptosis. Besides, up-regulation of BAX/BCL-2 ratio, and down-regulation of MCL-1 are also observed. Moreover, this combination inhibits IRAK1, NF-κB and ERK1/2 activation, and leads to down-regulation of inflammatory cytokines (IL6, IL8, CXCL1, CCL2), S100A7/9 and CSC-related genes (OCT4, SOX2, NANOG, ALDH1, CD44) expression. In addition, the combination treatment suppresses MB231-PR cell invasion ability, and impairs tumor sphere growth both in MB231-PR and SUM159 PTX resistant (SUM159-PR) cells. Conclusion Our study demonstrates that GPT can resensitize TNBC PTX resistant cells to PTX by inhibiting the IRAK1/NF-κB and ERK pathways and reducing stem cell characteristics. |
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| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T08:17:30Z |
| publishDate | 2020-06-01 |
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| spelling | doaj.art-432e3d1db9524c57a7b8c7d0749d0ed62023-12-02T22:00:24ZengPeerJ Inc.PeerJ2167-83592020-06-018e928110.7717/peerj.9281Ginsenoside panaxatriol reverses TNBC paclitaxel resistance by inhibiting the IRAK1/NF-κB and ERK pathwaysPanpan Wang0Dan Song1Danhong Wan2Lingyu Li3Wenhui Mei4Xiaoyun Li5Li Han6Xiaofeng Zhu7Li Yang8Yu Cai9Ronghua Zhang10College of Pharmacy, Jinan University, Guangzhou, ChinaCollege of Pharmacy, Jinan University, Guangzhou, ChinaCollege of Traditional Chinese Medicine, Jinan University, Guangzhou, ChinaCollege of Traditional Chinese Medicine, Jinan University, Guangzhou, ChinaCollege of Traditional Chinese Medicine, Jinan University, Guangzhou, ChinaCollege of Traditional Chinese Medicine, Jinan University, Guangzhou, ChinaFirst Affiliated Hospital of Jinan University, Guangzhou, ChinaFirst Affiliated Hospital of Jinan University, Guangzhou, ChinaCollege of Pharmacy, Jinan University, Guangzhou, ChinaCollege of Pharmacy, Jinan University, Guangzhou, ChinaCollege of Pharmacy, Jinan University, Guangzhou, ChinaBackground Paclitaxel (PTX) resistance is a major obstacle in the treatment of triple-negative breast cancer (TNBC). Previously, we have reported that interleukin-1 receptor-associated kinase 1 (IRAK1) and its downstream pathways are associated with PTX resistance in TNBC cells. In this study, we sought to investigate the combination treatment of ginsenoside panaxatriol (GPT), one of the main active components in Panax ginseng, with PTX on viability and apoptosis of TNBC PTX resistant cells, and explore the role of IRAK1 mediated signaling pathways in the therapeutic effects. Methods CellTiter-Glo and colony formation assays were used to assess cell viability. Flow cytometry was used to analyze subG1 and apoptosis. Western blot was used to detect expressions of proteins involved in apoptosis and the IRAK1/NF-κB and ERK pathways. The mRNA expression of inflammatory cytokines, S100A7/8/9 and cancer stem cell (CSC)-related genes were examined by qPCR. Stem cells were identified by tumor sphere assay. Cell invasion ability was examined by transwell assay. Results We show that GPT inhibits MDA-MB-231 PTX resistant (MB231-PR) cell viability in a dose-dependent manner. When combined with PTX, GPT synergistically causes more cell death, induces subG1 accumulation and cell apoptosis. Besides, up-regulation of BAX/BCL-2 ratio, and down-regulation of MCL-1 are also observed. Moreover, this combination inhibits IRAK1, NF-κB and ERK1/2 activation, and leads to down-regulation of inflammatory cytokines (IL6, IL8, CXCL1, CCL2), S100A7/9 and CSC-related genes (OCT4, SOX2, NANOG, ALDH1, CD44) expression. In addition, the combination treatment suppresses MB231-PR cell invasion ability, and impairs tumor sphere growth both in MB231-PR and SUM159 PTX resistant (SUM159-PR) cells. Conclusion Our study demonstrates that GPT can resensitize TNBC PTX resistant cells to PTX by inhibiting the IRAK1/NF-κB and ERK pathways and reducing stem cell characteristics.https://peerj.com/articles/9281.pdfTNBCPaclitaxel resistanceIRAK1/NF-κB pathwayERK pathwayGinsenoside panaxatriol |
| spellingShingle | Panpan Wang Dan Song Danhong Wan Lingyu Li Wenhui Mei Xiaoyun Li Li Han Xiaofeng Zhu Li Yang Yu Cai Ronghua Zhang Ginsenoside panaxatriol reverses TNBC paclitaxel resistance by inhibiting the IRAK1/NF-κB and ERK pathways PeerJ TNBC Paclitaxel resistance IRAK1/NF-κB pathway ERK pathway Ginsenoside panaxatriol |
| title | Ginsenoside panaxatriol reverses TNBC paclitaxel resistance by inhibiting the IRAK1/NF-κB and ERK pathways |
| title_full | Ginsenoside panaxatriol reverses TNBC paclitaxel resistance by inhibiting the IRAK1/NF-κB and ERK pathways |
| title_fullStr | Ginsenoside panaxatriol reverses TNBC paclitaxel resistance by inhibiting the IRAK1/NF-κB and ERK pathways |
| title_full_unstemmed | Ginsenoside panaxatriol reverses TNBC paclitaxel resistance by inhibiting the IRAK1/NF-κB and ERK pathways |
| title_short | Ginsenoside panaxatriol reverses TNBC paclitaxel resistance by inhibiting the IRAK1/NF-κB and ERK pathways |
| title_sort | ginsenoside panaxatriol reverses tnbc paclitaxel resistance by inhibiting the irak1 nf κb and erk pathways |
| topic | TNBC Paclitaxel resistance IRAK1/NF-κB pathway ERK pathway Ginsenoside panaxatriol |
| url | https://peerj.com/articles/9281.pdf |
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