Silibinin and Paclitaxel Cotreatment Significantly Suppress the Activity and Lung Metastasis of Triple Negative 4T1 Mammary Tumor Cell in Mice
The in vitro and in vivo bioactivities of silibinin (SB), paclitaxel (PTX) and SB and PTX in combination (SB+PTX) against murine metastatic mammary 4T1 cancer cell line were investigated. Isobologram and combination index (CI) analyses showed that SB and PTX can function synergistically in the inhib...
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| Format: | Article |
| Language: | English |
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Elsevier
2012-10-01
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| Series: | Journal of Traditional and Complementary Medicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S222541101630116X |
| _version_ | 1811216665082331136 |
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| author | Bing-Ying Ho Chun-Hung Lin Maria Karmella Apaya Wen-Wan Chao Lie-Fen Shyur |
| author_facet | Bing-Ying Ho Chun-Hung Lin Maria Karmella Apaya Wen-Wan Chao Lie-Fen Shyur |
| author_sort | Bing-Ying Ho |
| collection | DOAJ |
| description | The in vitro and in vivo bioactivities of silibinin (SB), paclitaxel (PTX) and SB and PTX in combination (SB+PTX) against murine metastatic mammary 4T1 cancer cell line were investigated. Isobologram and combination index (CI) analyses showed that SB and PTX can function synergistically in the inhibition of 4T1 cell proliferation with a CI value<1. Both SB and PTX alone or SB+PTX treatment inhibited 4T1 cell migration and motility possibly through downregulation of the serpin protease nexin-1 (PN-1) and N-cadherin expression, inhibition of matrix metalloprotease (MMP)-9 activity, and upregulation of E-cadherin. Flow cytometry and Western blot analyses demonstrated that both drugs deregulated cell-cycle mediators and induced apoptosis in 4T1 cells. A real-time in vivo bioluminescence imaging system to monitor the breast cancer cell metastasis in syngeneic BALB/c mice was established using a stable 4T1pGL−COX−2/Luc cell clone carrying a COX-2 promoter driven-luciferase reporter gene. In vivo study using the allograft 4T1pGL−COX−2/Luc metastatic mouse model indicated that SB co-treated with PTX can significantly suppress lung metastasis of 4T1 cells likely through inhibiting cell proliferation and angiogenesis. Together, this study demonstrates that SB could act synergistically with PTX in 4T1 cells, providing a therapeutic option for highly metastatic triple negative breast cancer. |
| first_indexed | 2024-04-12T06:42:05Z |
| format | Article |
| id | doaj.art-028d5c0330b14e47a7c74e92cce3bf5e |
| institution | Directory Open Access Journal |
| issn | 2225-4110 |
| language | English |
| last_indexed | 2024-04-12T06:42:05Z |
| publishDate | 2012-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Traditional and Complementary Medicine |
| spelling | doaj.art-028d5c0330b14e47a7c74e92cce3bf5e2022-12-22T03:43:40ZengElsevierJournal of Traditional and Complementary Medicine2225-41102012-10-012430131110.1016/S2225-4110(16)30116-XSilibinin and Paclitaxel Cotreatment Significantly Suppress the Activity and Lung Metastasis of Triple Negative 4T1 Mammary Tumor Cell in MiceBing-Ying Ho0Chun-Hung Lin1Maria Karmella Apaya2Wen-Wan Chao3Lie-Fen Shyur4Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, TaiwanAgricultural Biotechnology Research Center, Academia Sinica, Taipei 115, TaiwanAgricultural Biotechnology Research Center, Academia Sinica, Taipei 115, TaiwanAgricultural Biotechnology Research Center, Academia Sinica, Taipei 115, TaiwanAgricultural Biotechnology Research Center, Academia Sinica, Taipei 115, TaiwanThe in vitro and in vivo bioactivities of silibinin (SB), paclitaxel (PTX) and SB and PTX in combination (SB+PTX) against murine metastatic mammary 4T1 cancer cell line were investigated. Isobologram and combination index (CI) analyses showed that SB and PTX can function synergistically in the inhibition of 4T1 cell proliferation with a CI value<1. Both SB and PTX alone or SB+PTX treatment inhibited 4T1 cell migration and motility possibly through downregulation of the serpin protease nexin-1 (PN-1) and N-cadherin expression, inhibition of matrix metalloprotease (MMP)-9 activity, and upregulation of E-cadherin. Flow cytometry and Western blot analyses demonstrated that both drugs deregulated cell-cycle mediators and induced apoptosis in 4T1 cells. A real-time in vivo bioluminescence imaging system to monitor the breast cancer cell metastasis in syngeneic BALB/c mice was established using a stable 4T1pGL−COX−2/Luc cell clone carrying a COX-2 promoter driven-luciferase reporter gene. In vivo study using the allograft 4T1pGL−COX−2/Luc metastatic mouse model indicated that SB co-treated with PTX can significantly suppress lung metastasis of 4T1 cells likely through inhibiting cell proliferation and angiogenesis. Together, this study demonstrates that SB could act synergistically with PTX in 4T1 cells, providing a therapeutic option for highly metastatic triple negative breast cancer.http://www.sciencedirect.com/science/article/pii/S222541101630116XSilibininPaclitaxelTriple negative breast cancerLung metastasisSynergistic effect |
| spellingShingle | Bing-Ying Ho Chun-Hung Lin Maria Karmella Apaya Wen-Wan Chao Lie-Fen Shyur Silibinin and Paclitaxel Cotreatment Significantly Suppress the Activity and Lung Metastasis of Triple Negative 4T1 Mammary Tumor Cell in Mice Journal of Traditional and Complementary Medicine Silibinin Paclitaxel Triple negative breast cancer Lung metastasis Synergistic effect |
| title | Silibinin and Paclitaxel Cotreatment Significantly Suppress the Activity and Lung Metastasis of Triple Negative 4T1 Mammary Tumor Cell in Mice |
| title_full | Silibinin and Paclitaxel Cotreatment Significantly Suppress the Activity and Lung Metastasis of Triple Negative 4T1 Mammary Tumor Cell in Mice |
| title_fullStr | Silibinin and Paclitaxel Cotreatment Significantly Suppress the Activity and Lung Metastasis of Triple Negative 4T1 Mammary Tumor Cell in Mice |
| title_full_unstemmed | Silibinin and Paclitaxel Cotreatment Significantly Suppress the Activity and Lung Metastasis of Triple Negative 4T1 Mammary Tumor Cell in Mice |
| title_short | Silibinin and Paclitaxel Cotreatment Significantly Suppress the Activity and Lung Metastasis of Triple Negative 4T1 Mammary Tumor Cell in Mice |
| title_sort | silibinin and paclitaxel cotreatment significantly suppress the activity and lung metastasis of triple negative 4t1 mammary tumor cell in mice |
| topic | Silibinin Paclitaxel Triple negative breast cancer Lung metastasis Synergistic effect |
| url | http://www.sciencedirect.com/science/article/pii/S222541101630116X |
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