Curcumin inhibits proliferation of hepatocellular carcinoma cells by blocking PTPN1 and PTPN11 expression

姜黄素通过阻断 PTPN1 和 PTPN11 表达抑制肝癌细胞增殖

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作者:Jingru Zhang, Yang Liu, Xiaojie Wang, Zhiyi Wang, Enjia Xing, Jingmin Li, Dong Wang

Abstract

The antitumor mechanism of curcumin is unclear, especially in hepatocellular carcinoma (HCC) cells. To clarify the mechanism of action of curcumin in the effective treatment of HCC, the targets of curcumin were screened and validated. Candidate genes of curcumin for HCC were screened using the traditional Chinese medicine systems pharmacology (TCMSP) database and validated using The Cancer Genome Atlas (TCGA) database. The correlation of mRNA expression levels between key candidate genes was identified in the TCGA liver hepatocellular carcinoma (LIHC) dataset. The effects on prognosis were analyzed to identify the target gene of curcumin, which inhibits HCC cell proliferation. Based on the subcutaneous xenograft model of human HCC in nude mice, the expression levels of target proteins were observed using immunohistochemistry. The analysis results of the present study identified the target genes of curcumin, which were obtained by screening the TCSMP database. The protein tyrosine phosphatase non-receptor type 1 (PTPN1) was obtained from TCGA database analysis of the targeted genes. The expression levels of PTPN1 and its homologous sequence genes in TCGA LIHC project was analyzed to identify the potential target gene of curcumin, for use in HCC treatment. Next, xenograft experiments were performed to investigate the therapeutic effects of curcumin in an animal model. Curcumin was demonstrated to inhibit the growth of HCC xenograft tumors in mice. Immunohistochemistry results demonstrated that the protein expression levels of PTPN1 and PTPN11 in the curcumin group were significantly lower compared with those in the control group. In conclusion, these results demonstrated that curcumin inhibits the proliferation of HCC cells by inhibiting the expression of PTPN1 and PTPN11.

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