Yi Zhao, Linan Zhao, Tao Wang, Zhenghao Liu, Suyuan Tang, Hongxia Huang, Li Wu, Youzhi Sun
{"title":"基于RNA-Seq和IPA分析的中药复方舒肝解郁调控DMBA诱导的乳腺癌和乳腺癌细胞株的SNCG/ER-a/AKT-ERK通路","authors":"Yi Zhao, Linan Zhao, Tao Wang, Zhenghao Liu, Suyuan Tang, Hongxia Huang, Li Wu, Youzhi Sun","doi":"10.1177/15347354241233258","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Soothing the liver (called <i>Shu Gan Jie Yu</i> in Chinese, SGJY) is a significant therapeutic method for breast cancer in TCM. In this study, 3 liver-soothing herbs, including <i>Cyperus rotundus</i> L., <i>Citrus medica</i> L. var. <i>sarcodactylis</i> Swingle and <i>Rosa rugosa</i> Thunb. were selected and combined to form a SGJY herbal combinatory.</p><p><strong>The aim of the study: </strong>To investigate the inhibiting effect of SGJY on breast cancer in vivo and vitro, and to explore the potential mechanisms.</p><p><strong>Materials and methods: </strong>SGJY herbal combination was extracted using water. A breast cancer rat model was developed by chemical DMBA by gavage, then treated with SGJY for 11 weeks. The tumor tissue was preserved for RNA sequencing and analyzed by IPA software. The inhibition effects of SGJY on MCF-7 and T47D breast cancer cells were investigated by SRB assay and cell apoptosis analysis, and the protein expression levels of SNCG, ER-α, <i>p</i>-AKT and <i>p</i>-ERK were measured by western blotting.</p><p><strong>Results: </strong>SGJY significantly reduced the tumor weight and volume, and the level of estradiol in serum. The results of IPA analysis reveal SGJY upregulated 7 canonical pathways and downregulated 16 canonical pathways. Estrogen receptor signaling was the key canonical pathway with 9 genes downregulated. The results of upstream regulator analysis reveal beta-estradiol was the central target; the upstream regulator network scheme showed that 86 genes could affect the expression of the beta-estradiol, including SNCG, CCL21 and MB. Additionally, SGJY was verified to significantly alter the expression of SNCG mRNA, CCL21 mRNA and MB mRNA which was consistent with the data of RNA-Seq. The inhibition effects of SGJY exhibited a dose-dependent response. The apoptosis rates of MCF7 and T47D cells were upregulated. The protein expression of SNCG, ER-α, <i>p</i>-AKT and <i>p</i>-ERK were all significantly decreased by SGJY on MCF-7 and T47D cells.</p><p><strong>Conclusion: </strong>The results demonstrate that SGJY may inhibit the growth of breast cancer. The mechanism might involve downregulating the level of serum estradiol, and suppressing the protein expression in the SNCG/ER-α/AKT-ERK pathway.</p>","PeriodicalId":13734,"journal":{"name":"Integrative Cancer Therapies","volume":"23 ","pages":"15347354241233258"},"PeriodicalIF":2.9000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10878215/pdf/","citationCount":"0","resultStr":"{\"title\":\"The Herbal Combination Shu Gan Jie Yu Regulates the SNCG/ER-a/AKT-ERK Pathway in DMBA-Induced Breast Cancer and Breast Cancer Cell Lines Based on RNA-Seq and IPA Analysis.\",\"authors\":\"Yi Zhao, Linan Zhao, Tao Wang, Zhenghao Liu, Suyuan Tang, Hongxia Huang, Li Wu, Youzhi Sun\",\"doi\":\"10.1177/15347354241233258\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Soothing the liver (called <i>Shu Gan Jie Yu</i> in Chinese, SGJY) is a significant therapeutic method for breast cancer in TCM. In this study, 3 liver-soothing herbs, including <i>Cyperus rotundus</i> L., <i>Citrus medica</i> L. var. <i>sarcodactylis</i> Swingle and <i>Rosa rugosa</i> Thunb. were selected and combined to form a SGJY herbal combinatory.</p><p><strong>The aim of the study: </strong>To investigate the inhibiting effect of SGJY on breast cancer in vivo and vitro, and to explore the potential mechanisms.</p><p><strong>Materials and methods: </strong>SGJY herbal combination was extracted using water. A breast cancer rat model was developed by chemical DMBA by gavage, then treated with SGJY for 11 weeks. The tumor tissue was preserved for RNA sequencing and analyzed by IPA software. The inhibition effects of SGJY on MCF-7 and T47D breast cancer cells were investigated by SRB assay and cell apoptosis analysis, and the protein expression levels of SNCG, ER-α, <i>p</i>-AKT and <i>p</i>-ERK were measured by western blotting.</p><p><strong>Results: </strong>SGJY significantly reduced the tumor weight and volume, and the level of estradiol in serum. The results of IPA analysis reveal SGJY upregulated 7 canonical pathways and downregulated 16 canonical pathways. Estrogen receptor signaling was the key canonical pathway with 9 genes downregulated. The results of upstream regulator analysis reveal beta-estradiol was the central target; the upstream regulator network scheme showed that 86 genes could affect the expression of the beta-estradiol, including SNCG, CCL21 and MB. Additionally, SGJY was verified to significantly alter the expression of SNCG mRNA, CCL21 mRNA and MB mRNA which was consistent with the data of RNA-Seq. The inhibition effects of SGJY exhibited a dose-dependent response. The apoptosis rates of MCF7 and T47D cells were upregulated. The protein expression of SNCG, ER-α, <i>p</i>-AKT and <i>p</i>-ERK were all significantly decreased by SGJY on MCF-7 and T47D cells.</p><p><strong>Conclusion: </strong>The results demonstrate that SGJY may inhibit the growth of breast cancer. The mechanism might involve downregulating the level of serum estradiol, and suppressing the protein expression in the SNCG/ER-α/AKT-ERK pathway.</p>\",\"PeriodicalId\":13734,\"journal\":{\"name\":\"Integrative Cancer Therapies\",\"volume\":\"23 \",\"pages\":\"15347354241233258\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10878215/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Integrative Cancer Therapies\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/15347354241233258\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"INTEGRATIVE & COMPLEMENTARY MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Integrative Cancer Therapies","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/15347354241233258","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"INTEGRATIVE & COMPLEMENTARY MEDICINE","Score":null,"Total":0}
The Herbal Combination Shu Gan Jie Yu Regulates the SNCG/ER-a/AKT-ERK Pathway in DMBA-Induced Breast Cancer and Breast Cancer Cell Lines Based on RNA-Seq and IPA Analysis.
Background: Soothing the liver (called Shu Gan Jie Yu in Chinese, SGJY) is a significant therapeutic method for breast cancer in TCM. In this study, 3 liver-soothing herbs, including Cyperus rotundus L., Citrus medica L. var. sarcodactylis Swingle and Rosa rugosa Thunb. were selected and combined to form a SGJY herbal combinatory.
The aim of the study: To investigate the inhibiting effect of SGJY on breast cancer in vivo and vitro, and to explore the potential mechanisms.
Materials and methods: SGJY herbal combination was extracted using water. A breast cancer rat model was developed by chemical DMBA by gavage, then treated with SGJY for 11 weeks. The tumor tissue was preserved for RNA sequencing and analyzed by IPA software. The inhibition effects of SGJY on MCF-7 and T47D breast cancer cells were investigated by SRB assay and cell apoptosis analysis, and the protein expression levels of SNCG, ER-α, p-AKT and p-ERK were measured by western blotting.
Results: SGJY significantly reduced the tumor weight and volume, and the level of estradiol in serum. The results of IPA analysis reveal SGJY upregulated 7 canonical pathways and downregulated 16 canonical pathways. Estrogen receptor signaling was the key canonical pathway with 9 genes downregulated. The results of upstream regulator analysis reveal beta-estradiol was the central target; the upstream regulator network scheme showed that 86 genes could affect the expression of the beta-estradiol, including SNCG, CCL21 and MB. Additionally, SGJY was verified to significantly alter the expression of SNCG mRNA, CCL21 mRNA and MB mRNA which was consistent with the data of RNA-Seq. The inhibition effects of SGJY exhibited a dose-dependent response. The apoptosis rates of MCF7 and T47D cells were upregulated. The protein expression of SNCG, ER-α, p-AKT and p-ERK were all significantly decreased by SGJY on MCF-7 and T47D cells.
Conclusion: The results demonstrate that SGJY may inhibit the growth of breast cancer. The mechanism might involve downregulating the level of serum estradiol, and suppressing the protein expression in the SNCG/ER-α/AKT-ERK pathway.
期刊介绍：
ICT is the first journal to spearhead and focus on a new and growing movement in cancer treatment. The journal emphasizes scientific understanding of alternative medicine and traditional medicine therapies, and their responsible integration with conventional health care. Integrative care includes therapeutic interventions in diet, lifestyle, exercise, stress care, and nutritional supplements, as well as experimental vaccines, chrono-chemotherapy, and other advanced treatments. Contributors are leading oncologists, researchers, nurses, and health-care professionals.
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