The transdermal cream of Formestane anti-breast cancer by controlling PI3K-Akt pathway and the tumor immune microenvironment
BackgroundTreatment of ER+ breast cancer with intramuscular formulation of Formestane (4-OHA) shrinks the tumor within weeks. Since the tedious way of intramuscular administration and side effects are not suited for adjuvant treatment, Formestane was withdrawn from the market. A new transdermal form...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1041525/full |
| _version_ | 1797858543535128576 |
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| author | Lanyang Gao Lei Zhu Chen Shen Xiaoming Hou Youyou Chen Linglin Zou Huiyan Qiang Alexander T. Teichmann Wenguang Fu Yao Luo |
| author_facet | Lanyang Gao Lei Zhu Chen Shen Xiaoming Hou Youyou Chen Linglin Zou Huiyan Qiang Alexander T. Teichmann Wenguang Fu Yao Luo |
| author_sort | Lanyang Gao |
| collection | DOAJ |
| description | BackgroundTreatment of ER+ breast cancer with intramuscular formulation of Formestane (4-OHA) shrinks the tumor within weeks. Since the tedious way of intramuscular administration and side effects are not suited for adjuvant treatment, Formestane was withdrawn from the market. A new transdermal formulation of 4-OHA cream may overcome the defects and retain the effect of shrinking the breast cancer tumor. However, the effects of 4-OHA cream on breast cancer need further confirmatory studies.MethodsIn this work, in vivo, the influence of 4-OHA cream on breast cancer was evaluated using the mode of 7,12-dimethylbenz(a)anthracene (DMBA) induced rat mammary cancer. We explored the common molecule mechanisms of action of 4-OHA cream and its injection formulation on breast cancer through RNA- sequencing-based transcriptome analysis and several biochemical experiments.ResultsThe results showed that the cream substantially reduced the entire quantity, size, and volum of tumors in DMBA-treated rats consistent with 4-OHA injection, and indicated that there were comprehensive signals involved in 4-OHA antitumor activity, such as ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, and proteoglycans in cancer. In addition, we observed that both 4-OHA formulations could enhance immune infiltration, especially CD8+ T cells, B cells, natural killer cells, and macrophages infiltration, in the DMBA-induced mammary tumor tissues. The antitumor effects of 4-OHA partly depended on these immune cells.Conclusion4-OHA cream could inhibit breast cancer growth as its injection formulation and may provide a new way for neoadjuvant treatment of ER+ breast cancer. |
| first_indexed | 2024-04-09T21:15:04Z |
| format | Article |
| id | doaj.art-56f69796d2e2471c9b93c00b7b62cf02 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-09T21:15:04Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-56f69796d2e2471c9b93c00b7b62cf022023-03-28T10:20:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-03-011410.3389/fimmu.2023.10415251041525The transdermal cream of Formestane anti-breast cancer by controlling PI3K-Akt pathway and the tumor immune microenvironmentLanyang Gao0Lei Zhu1Chen Shen2Xiaoming Hou3Youyou Chen4Linglin Zou5Huiyan Qiang6Alexander T. Teichmann7Wenguang Fu8Yao Luo9Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, ChinaWest China Hospital, Sichuan University, Chengdu, ChinaWest China Hospital, Sichuan University, Chengdu, ChinaWest China Hospital, Sichuan University, Chengdu, ChinaAcademician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, ChinaAcademician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, ChinaAcademician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, ChinaSichuan Provincial Center for Gynaecology and Breast Disease, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, ChinaAcademician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, ChinaWest China Hospital, Sichuan University, Chengdu, ChinaBackgroundTreatment of ER+ breast cancer with intramuscular formulation of Formestane (4-OHA) shrinks the tumor within weeks. Since the tedious way of intramuscular administration and side effects are not suited for adjuvant treatment, Formestane was withdrawn from the market. A new transdermal formulation of 4-OHA cream may overcome the defects and retain the effect of shrinking the breast cancer tumor. However, the effects of 4-OHA cream on breast cancer need further confirmatory studies.MethodsIn this work, in vivo, the influence of 4-OHA cream on breast cancer was evaluated using the mode of 7,12-dimethylbenz(a)anthracene (DMBA) induced rat mammary cancer. We explored the common molecule mechanisms of action of 4-OHA cream and its injection formulation on breast cancer through RNA- sequencing-based transcriptome analysis and several biochemical experiments.ResultsThe results showed that the cream substantially reduced the entire quantity, size, and volum of tumors in DMBA-treated rats consistent with 4-OHA injection, and indicated that there were comprehensive signals involved in 4-OHA antitumor activity, such as ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, and proteoglycans in cancer. In addition, we observed that both 4-OHA formulations could enhance immune infiltration, especially CD8+ T cells, B cells, natural killer cells, and macrophages infiltration, in the DMBA-induced mammary tumor tissues. The antitumor effects of 4-OHA partly depended on these immune cells.Conclusion4-OHA cream could inhibit breast cancer growth as its injection formulation and may provide a new way for neoadjuvant treatment of ER+ breast cancer.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1041525/fullFormestane creamDMBA-induced mammary cancerPI3K-Akt signaling pathwaytumor immune microenvironmentRNA transcriptome sequencing |
| spellingShingle | Lanyang Gao Lei Zhu Chen Shen Xiaoming Hou Youyou Chen Linglin Zou Huiyan Qiang Alexander T. Teichmann Wenguang Fu Yao Luo The transdermal cream of Formestane anti-breast cancer by controlling PI3K-Akt pathway and the tumor immune microenvironment Frontiers in Immunology Formestane cream DMBA-induced mammary cancer PI3K-Akt signaling pathway tumor immune microenvironment RNA transcriptome sequencing |
| title | The transdermal cream of Formestane anti-breast cancer by controlling PI3K-Akt pathway and the tumor immune microenvironment |
| title_full | The transdermal cream of Formestane anti-breast cancer by controlling PI3K-Akt pathway and the tumor immune microenvironment |
| title_fullStr | The transdermal cream of Formestane anti-breast cancer by controlling PI3K-Akt pathway and the tumor immune microenvironment |
| title_full_unstemmed | The transdermal cream of Formestane anti-breast cancer by controlling PI3K-Akt pathway and the tumor immune microenvironment |
| title_short | The transdermal cream of Formestane anti-breast cancer by controlling PI3K-Akt pathway and the tumor immune microenvironment |
| title_sort | transdermal cream of formestane anti breast cancer by controlling pi3k akt pathway and the tumor immune microenvironment |
| topic | Formestane cream DMBA-induced mammary cancer PI3K-Akt signaling pathway tumor immune microenvironment RNA transcriptome sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1041525/full |
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