Sophocarpine can enhance the inhibiting effect of oxaliplatin on colon cancer liver metastasis-in vitro and in vivo.

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.