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Curcumin inhibits proliferation of hepatocellular carcinoma cells by blocking PTPN1 and PTPN11 expression
Jingru Zhang1, Yang Liu1, Xiaojie Wang2
1Department of Histology and Embryology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
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.
Insights
Curcumin inhibits liver cancer (HCC) cell growth by targeting protein tyrosine phosphatases PTPN1 and PTPN11. This study clarifies curcumin's antitumor mechanism in HCC, identifying key molecular targets for potential therapeutic strategies.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- The precise antitumor mechanism of curcumin remains unclear, particularly in hepatocellular carcinoma (HCC).
- Understanding curcumin's molecular targets is crucial for its effective application in HCC treatment.
- Identifying specific genes and proteins affected by curcumin can elucidate its therapeutic potential.
Purpose of the Study:
- To screen and validate the molecular targets of curcumin in hepatocellular carcinoma (HCC).
- To investigate the mechanism by which curcumin inhibits HCC cell proliferation.
- To evaluate the therapeutic efficacy of curcumin in an in vivo HCC model.
Main Methods:
- Candidate genes were identified using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database.
- Gene validation and expression analysis were performed using The Cancer Genome Atlas (TCGA) database (LIHC dataset).
- In vivo studies utilized a subcutaneous xenograft model of human HCC in nude mice, with immunohistochemistry to assess protein expression.
Main Results:
- The protein tyrosine phosphatase non-receptor type 1 (PTPN1) was identified as a key target gene.
- Curcumin significantly inhibited the growth of HCC xenograft tumors in mice.
- Immunohistochemistry revealed significantly lower protein expression levels of PTPN1 and PTPN11 in curcumin-treated mice compared to controls.
Conclusions:
- Curcumin inhibits HCC cell proliferation by downregulating the expression of PTPN1 and PTPN11.
- These findings clarify curcumin's antitumor mechanism in HCC.
- PTPN1 and PTPN11 represent potential therapeutic targets for curcumin-based HCC treatment.
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