Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT
Abstract Background Novel chemotherapeutic drugs with good anti-tumor activity are of pressing need for bladder cancer treatment. In this study, plumbagin (PL), a natural plant-derived drug extracted from Chinese herbals, was identified as a promising candidate for human bladder cancer (BCa) chemoth...
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| Format: | Article |
| Language: | English |
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BMC
2020-10-01
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| Series: | Cancer Cell International |
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| Online Access: | http://link.springer.com/article/10.1186/s12935-020-01607-y |
| _version_ | 1818316533078687744 |
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| author | Renjie Zhang Zijian Wang Wenjie You Fengfang Zhou Zicheng Guo Kaiyu Qian Yu Xiao Xinghuan Wang |
| author_facet | Renjie Zhang Zijian Wang Wenjie You Fengfang Zhou Zicheng Guo Kaiyu Qian Yu Xiao Xinghuan Wang |
| author_sort | Renjie Zhang |
| collection | DOAJ |
| description | Abstract Background Novel chemotherapeutic drugs with good anti-tumor activity are of pressing need for bladder cancer treatment. In this study, plumbagin (PL), a natural plant-derived drug extracted from Chinese herbals, was identified as a promising candidate for human bladder cancer (BCa) chemotherapy. Methods The anti-tumor activity of PL was evaluated using a series of in vitro experiments, such as MTT, transwell assay, flow cytometry, quantitative real-time PCR (qRT-PCR) and western blotting. We established xenograft tumors in nude mice by subcutaneous injection with the human bladder cancer T24 cells. Results The results showed that PL could inhibit the proliferation, migration and survival of BCa cells (T24 and UMUC3 cells) in a time- and dose-dependent way. We found PL promotes the cell cycle arrest and apoptosis by inhibiting PI3K/AKT/mTOR signaling pathway, which inhibits cell proliferation. In vivo, anti-tumor activity of PL was further investigated using a BCa cell xenograft mice model. To simulate clinical chemotherapy, the PL were intravenously injected with a dose of 10 mg/kg for 10 times. Compared with the blank control, the tumor weight in PL treated group decreased significantly from 0.57 ± 0.04 g to 0.21 ± 0.06 g (P < 0.001). Conclusions In our study. We found PL inhibits the proliferation of T24 and UMUC3 cells in vivo and in vitro, which may play a role through several downstream effectors of PI3K/AKT/mTOR signaling pathway to promote the cell cycle arrest and apoptosis. Meanwhile, we consider that PL may inhibit the migration of bladder cancer cells via EMT suppression and induce ROS generation to make cell apoptosis. This work screened out a novel chemotherapeutic drug (plumbagin) with relatively good anti-tumor activity, which possessed great potential in BCa chemotherapy. |
| first_indexed | 2024-12-13T09:22:56Z |
| format | Article |
| id | doaj.art-add6473cc0de414a82915196df91ff12 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-13T09:22:56Z |
| publishDate | 2020-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-add6473cc0de414a82915196df91ff122022-12-21T23:52:42ZengBMCCancer Cell International1475-28672020-10-0120111710.1186/s12935-020-01607-ySuppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMTRenjie Zhang0Zijian Wang1Wenjie You2Fengfang Zhou3Zicheng Guo4Kaiyu Qian5Yu Xiao6Xinghuan Wang7Department of Urology, Zhongnan Hospital of Wuhan UniversityDepartment of Urology, Zhongnan Hospital of Wuhan UniversityDepartment of Urology, Zhongnan Hospital of Wuhan UniversityDepartment of Urology, Zhongnan Hospital of Wuhan UniversityDepartment of Urology, The Central Hospital of Enshi Tujia and Miao Autonomous PrefectureDepartment of Urology, Zhongnan Hospital of Wuhan UniversityDepartment of Biological Repositories, Zhongnan Hospital of Wuhan UniversityDepartment of Urology, Zhongnan Hospital of Wuhan UniversityAbstract Background Novel chemotherapeutic drugs with good anti-tumor activity are of pressing need for bladder cancer treatment. In this study, plumbagin (PL), a natural plant-derived drug extracted from Chinese herbals, was identified as a promising candidate for human bladder cancer (BCa) chemotherapy. Methods The anti-tumor activity of PL was evaluated using a series of in vitro experiments, such as MTT, transwell assay, flow cytometry, quantitative real-time PCR (qRT-PCR) and western blotting. We established xenograft tumors in nude mice by subcutaneous injection with the human bladder cancer T24 cells. Results The results showed that PL could inhibit the proliferation, migration and survival of BCa cells (T24 and UMUC3 cells) in a time- and dose-dependent way. We found PL promotes the cell cycle arrest and apoptosis by inhibiting PI3K/AKT/mTOR signaling pathway, which inhibits cell proliferation. In vivo, anti-tumor activity of PL was further investigated using a BCa cell xenograft mice model. To simulate clinical chemotherapy, the PL were intravenously injected with a dose of 10 mg/kg for 10 times. Compared with the blank control, the tumor weight in PL treated group decreased significantly from 0.57 ± 0.04 g to 0.21 ± 0.06 g (P < 0.001). Conclusions In our study. We found PL inhibits the proliferation of T24 and UMUC3 cells in vivo and in vitro, which may play a role through several downstream effectors of PI3K/AKT/mTOR signaling pathway to promote the cell cycle arrest and apoptosis. Meanwhile, we consider that PL may inhibit the migration of bladder cancer cells via EMT suppression and induce ROS generation to make cell apoptosis. This work screened out a novel chemotherapeutic drug (plumbagin) with relatively good anti-tumor activity, which possessed great potential in BCa chemotherapy.http://link.springer.com/article/10.1186/s12935-020-01607-yPlumbaginBladder cancerPI3K/AKT/mTORCell cycleApoptosis |
| spellingShingle | Renjie Zhang Zijian Wang Wenjie You Fengfang Zhou Zicheng Guo Kaiyu Qian Yu Xiao Xinghuan Wang Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT Cancer Cell International Plumbagin Bladder cancer PI3K/AKT/mTOR Cell cycle Apoptosis |
| title | Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT |
| title_full | Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT |
| title_fullStr | Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT |
| title_full_unstemmed | Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT |
| title_short | Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT |
| title_sort | suppressive effects of plumbagin on the growth of human bladder cancer cells via pi3k akt mtor signaling pathways and emt |
| topic | Plumbagin Bladder cancer PI3K/AKT/mTOR Cell cycle Apoptosis |
| url | http://link.springer.com/article/10.1186/s12935-020-01607-y |
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