Abstract
To determine whether sophocarpine (SC) can enhance the inhibiting effect of oxaliplatin on colorectal cancer (CRC) liver metastasis (CRCLM)—in vitro and in vivo. The inhibitory effect of SC and/or oxaliplatin on the proliferation, invasion, and migration of CRC cells was determined by CCK-8, MTT, wound healing migration, and transwell assay. Western blot and immunohistochemistry were used to evaluate the inhibitory effect of SC and/or oxaliplatin on the epithelial-mesenchymal transition (EMT) process. Nude mouse models of human CRCLM were established to test the anti-metastasis effect of SC and oxaliplatin in the single or combined form. SC exerted an inhibitory effect on the proliferation, invasion, and migration of CRC cells both in vitro and in vivo. The combination index of SC and oxaliplatin was 0.58. In addition, the inhibitory effect of SC in combination with oxaliplatin was found to be significantly stronger compared with that mediated by either SC or oxaliplatin alone, suggesting that SC can effectively enhance the inhibitory effect of oxaliplatin on CRCLM both in vitro and in vivo. SC was also revealed to reverse EMT process in cell lines and tissues, as reflected by the observed downregulation of N-cadherin and vimentin expression and the upregulation of E-cadherin expression. Taken together, data from the present study suggest that SC administration can inhibit CRC cell proliferation, invasion, migration, and EMT, while enhancing the inhibitory effects of oxaliplatin both in vitro and in vivo. These findings indicate (that) SC to be a promising anti-metastasis agent for CRCLM.
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This study was supported by Liaoning Provincial Natural Science Foundations of China (grant nos. 201602037).
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XFZ designed the outline of the study. YSY and DW designed the study and conducted experiments. YSY wrote the manuscript. XFZ supervised the study, contributed to data acquisition, and revised the manuscript. YSY and DW collected and analyzed the data. All authors have read and approved the final version of this manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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The study protocol was authorized by the Ethics Committee of Dalian University Affiliated Xinhua Hospital (Dalian, China). All animal procedures were approved by the Institutional Animal Care Committee of Dalian University Affiliated Xinhua Hospital (Dalian, China).
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Yang, YS., Wen, D. & Zhao, XF. Sophocarpine can enhance the inhibiting effect of oxaliplatin on colon cancer liver metastasis—in vitro and in vivo. Naunyn-Schmiedeberg's Arch Pharmacol 394, 1263–1274 (2021). https://doi.org/10.1007/s00210-020-02032-8
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DOI: https://doi.org/10.1007/s00210-020-02032-8