Tanshinone IIA inhibits proliferation and migration by downregulation of the PI3K/Akt pathway in small cell lung cancer cells
Abstract Background Small cell lung cancer (SCLC) is the most malignant lung cancer type. Due to the high rates of metastasis and drug resistance, effective therapeutic strategies remain lacking. Tanshinone IIA (Tan IIA) has been reported to exhibit anti-tumor activity. Therefore, this study investi...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | BMC Complementary Medicine and Therapies |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12906-024-04363-y |
| _version_ | 1797275927363715072 |
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| author | Yuxin Jiang Yanli Bi Lingjie Zhou Senwen Zheng Tingting Jian Jian Chen |
| author_facet | Yuxin Jiang Yanli Bi Lingjie Zhou Senwen Zheng Tingting Jian Jian Chen |
| author_sort | Yuxin Jiang |
| collection | DOAJ |
| description | Abstract Background Small cell lung cancer (SCLC) is the most malignant lung cancer type. Due to the high rates of metastasis and drug resistance, effective therapeutic strategies remain lacking. Tanshinone IIA (Tan IIA) has been reported to exhibit anti-tumor activity. Therefore, this study investigated the ability and underlying mechanism of Tan IIA to inhibit the metastasis and proliferation of SCLC. Methods H1688 and H446 cells were treated in vitro with Tan IIA (0, 1, 2 and 4 µM) or LY294002 (10 µM) for 24, 48, 72 h. H1688 and H446 cell migration was evaluated in wound healing and transwell migration assays. RNA-sequencing helped assess gene expression. BALB/c nude mice were injected with H1688 cells and treated with the Tan IIA group (10 mg/kg/day) or a control. Expression of E-cadherin, vimentin and PI3K/Akt signaling pathway proteins in tumors and H1688 was investigated by immunohistochemical analysis and western blot. Results Tan IIA inhibited H1688 and H446 cell proliferation without inducing apoptosis and suppressed H1688 and H446 cell migration. E-cadherin expression was increased, while vimentin expression was reduced after administration of Tan IIA. RNA-sequencing revealed that some genes related with the PI3K/Akt signaling pathway were altered using Tan IIA treatment. Furthermore, western blot helped detect PI3K and p-Akt expression was also reduced by Tan IIA treatment. Tan IIA inhibited tumor growth in vivo. Moreover, Tan IIA increased tumoral expression of E-cadherin accompanied by PI3K and p-Akt downregulation. Conclusion Tan IIA suppresses SCLC proliferation and metastasis by inhibiting the PI3K/Akt signaling pathway, thereby highlighting the potential of Tan IIA as a new and relatively safe drug candidate to treat SCLC. |
| first_indexed | 2024-03-07T15:20:04Z |
| format | Article |
| id | doaj.art-8539bb959dc04e93a7e6efee5a77f41a |
| institution | Directory Open Access Journal |
| issn | 2662-7671 |
| language | English |
| last_indexed | 2024-03-07T15:20:04Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Complementary Medicine and Therapies |
| spelling | doaj.art-8539bb959dc04e93a7e6efee5a77f41a2024-03-05T17:40:58ZengBMCBMC Complementary Medicine and Therapies2662-76712024-01-0124111110.1186/s12906-024-04363-yTanshinone IIA inhibits proliferation and migration by downregulation of the PI3K/Akt pathway in small cell lung cancer cellsYuxin Jiang0Yanli Bi1Lingjie Zhou2Senwen Zheng3Tingting Jian4Jian Chen5School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical CollegeDepartment of Clinical Laboratorial Examination, Air Force Hangzhou Special Service Recuperation Center Sanatorium Area 3School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical CollegeSchool of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical CollegeSchool of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical CollegeSchool of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical CollegeAbstract Background Small cell lung cancer (SCLC) is the most malignant lung cancer type. Due to the high rates of metastasis and drug resistance, effective therapeutic strategies remain lacking. Tanshinone IIA (Tan IIA) has been reported to exhibit anti-tumor activity. Therefore, this study investigated the ability and underlying mechanism of Tan IIA to inhibit the metastasis and proliferation of SCLC. Methods H1688 and H446 cells were treated in vitro with Tan IIA (0, 1, 2 and 4 µM) or LY294002 (10 µM) for 24, 48, 72 h. H1688 and H446 cell migration was evaluated in wound healing and transwell migration assays. RNA-sequencing helped assess gene expression. BALB/c nude mice were injected with H1688 cells and treated with the Tan IIA group (10 mg/kg/day) or a control. Expression of E-cadherin, vimentin and PI3K/Akt signaling pathway proteins in tumors and H1688 was investigated by immunohistochemical analysis and western blot. Results Tan IIA inhibited H1688 and H446 cell proliferation without inducing apoptosis and suppressed H1688 and H446 cell migration. E-cadherin expression was increased, while vimentin expression was reduced after administration of Tan IIA. RNA-sequencing revealed that some genes related with the PI3K/Akt signaling pathway were altered using Tan IIA treatment. Furthermore, western blot helped detect PI3K and p-Akt expression was also reduced by Tan IIA treatment. Tan IIA inhibited tumor growth in vivo. Moreover, Tan IIA increased tumoral expression of E-cadherin accompanied by PI3K and p-Akt downregulation. Conclusion Tan IIA suppresses SCLC proliferation and metastasis by inhibiting the PI3K/Akt signaling pathway, thereby highlighting the potential of Tan IIA as a new and relatively safe drug candidate to treat SCLC.https://doi.org/10.1186/s12906-024-04363-yTanshinone IIASmall cell lung cancerMetastasisEpithelial-to-mesenchymal transitionPI3KAkt |
| spellingShingle | Yuxin Jiang Yanli Bi Lingjie Zhou Senwen Zheng Tingting Jian Jian Chen Tanshinone IIA inhibits proliferation and migration by downregulation of the PI3K/Akt pathway in small cell lung cancer cells BMC Complementary Medicine and Therapies Tanshinone IIA Small cell lung cancer Metastasis Epithelial-to-mesenchymal transition PI3K Akt |
| title | Tanshinone IIA inhibits proliferation and migration by downregulation of the PI3K/Akt pathway in small cell lung cancer cells |
| title_full | Tanshinone IIA inhibits proliferation and migration by downregulation of the PI3K/Akt pathway in small cell lung cancer cells |
| title_fullStr | Tanshinone IIA inhibits proliferation and migration by downregulation of the PI3K/Akt pathway in small cell lung cancer cells |
| title_full_unstemmed | Tanshinone IIA inhibits proliferation and migration by downregulation of the PI3K/Akt pathway in small cell lung cancer cells |
| title_short | Tanshinone IIA inhibits proliferation and migration by downregulation of the PI3K/Akt pathway in small cell lung cancer cells |
| title_sort | tanshinone iia inhibits proliferation and migration by downregulation of the pi3k akt pathway in small cell lung cancer cells |
| topic | Tanshinone IIA Small cell lung cancer Metastasis Epithelial-to-mesenchymal transition PI3K Akt |
| url | https://doi.org/10.1186/s12906-024-04363-y |
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