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sophocarpine 能增强奥沙利铂对结直肠癌肝转移的抑制作用:体内外研究。

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

机构信息

Department of General Surgery, Dalian University Affiliated Xinhua Hospital, Dalian, 116021, China.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2021 Jun;394(6):1263-1274. doi: 10.1007/s00210-020-02032-8. Epub 2021 Jan 6.

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.

摘要

目的

探讨苦参碱(SC)能否增强奥沙利铂(OXA)对结直肠癌肝转移(CRCLM)的抑制作用——体外和体内。

方法

CCK-8、MTT、划痕愈合迁移和Transwell 检测分别评估 SC 和/或 OXA 对 CRC 细胞增殖、侵袭和迁移的抑制作用。Western blot 和免疫组化检测 SC 和/或 OXA 对上皮间质转化(EMT)过程的抑制作用。建立人 CRCLM 裸鼠模型,以检测 SC 和 OXA 单药或联合应用的抗转移作用。

结果

SC 在体外和体内均能抑制 CRC 细胞的增殖、侵袭和迁移。SC 和 OXA 的联合指数为 0.58。此外,与单独使用 SC 或 OXA 相比,SC 联合 OXA 的抑制作用明显更强,表明 SC 能有效增强 OXA 对 CRCLM 的抑制作用——无论是在体外还是体内。SC 还能在细胞系和组织中逆转 EMT 过程,表现为 N-钙黏蛋白和波形蛋白表达下调,E-钙黏蛋白表达上调。

结论

SC 可抑制 CRC 细胞增殖、侵袭、迁移和 EMT,并增强 OXA 的抑制作用——无论是在体外还是体内,这表明 SC 可能是治疗 CRCLM 的一种有前途的抗转移药物。

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