Silibinin inhibits endometrial carcinoma via blocking pathways of STAT3 activation and SREBP1-mediated lipid
Zhengzheng Shi1, Qing Zhou1, Shuhong Gao2
1Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, PR China; Key Laboratory of Gynecologic Oncology of Shandong Province, Jinan, Shandong 250012, PR China; Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR China.
Aims:
To seek new conservative treatments for young women with early-stage endometrial carcinoma (EC) who desire to retain fertility, we investigated the effects and the underlying mechanism of silibinin in EC, which exhibits promising anti-cancer and tumour-suppressing properties in many malignant tumours.
Main Methods:
Through relevant experiments such as MTT assay, cell colony formation assay and subcutaneous xenograft experiment, we showed that silibinin inhibited the proliferation of EC cells and tumours. Silibinin significantly induced cell cycle arrest and promoted apoptosis in vitro. In vivo TUNEL assay confirmed the apoptotic effect caused by silibinin. STAT3 is activated in the development of tumours. Silibinin notably inhibited the expression of STAT3 phosphorylation and regulated the expression of downstream genes involved in cell cycle and apoptosis at protein and mRNA levels in EC cells. Furthermore, silibinin decreased the expression of intranuclear SREBP1, which is a key regulator of lipid metabolism in the nucleus, and reduced the lipid accumulation in EC cells. Downregulation of the expression levels of SREBP1 and its downstream genes associated with lipid metabolism was also observed in silibinin-treated EC cells.
Key Findings:
The results revealed that a novel anticancer drug, silibinin, markedly suppressed cell proliferation, cell cycle progression, apoptosis inhibition and lipid accumulation by blocking STAT3 and SERBP1 signalling pathways in EC cells.
Significance:
Silibinin has anti-tumour characteristics and inhibits abnormal lipid metabolism in EC. This compound is expected to contribute to the conservative and adjuvant treatment of EC and should therefore be investigated further.
Insights
Silibinin effectively inhibits endometrial carcinoma (EC) cell growth and promotes apoptosis by blocking STAT3 and SREBP1 pathways. This natural compound shows potential for fertility-sparing treatments in young women with early-stage EC.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Endometrial carcinoma (EC) poses a challenge for young women desiring fertility preservation.
- Existing treatments may impact fertility, necessitating novel, conservative therapeutic options.
- Silibinin, a natural compound, demonstrates anti-cancer properties in various malignancies.
Purpose of the Study:
- To investigate the anti-cancer effects of silibinin on endometrial carcinoma (EC).
- To elucidate the underlying molecular mechanisms of silibinin's action in EC.
- To evaluate silibinin as a potential fertility-sparing treatment for early-stage EC.
Main Methods:
- In vitro assays (MTT, colony formation) and in vivo xenograft models were used to assess silibinin's impact on EC cell proliferation and tumor growth.
- Cell cycle arrest and apoptosis were analyzed using specific assays.
- Western blotting and qRT-PCR were employed to examine the expression of STAT3, SREBP1, and their downstream targets at protein and mRNA levels.
Main Results:
- Silibinin significantly inhibited EC cell proliferation and tumor growth in vitro and in vivo.
- Silibinin induced cell cycle arrest and promoted apoptosis in EC cells.
- The compound suppressed STAT3 phosphorylation and downregulated SREBP1 expression, impacting lipid metabolism and downstream gene expression.
Conclusions:
- Silibinin exhibits significant anti-tumour activity against endometrial carcinoma.
- It effectively inhibits proliferation and induces apoptosis by targeting STAT3 and SREBP1 signaling pathways.
- Silibinin demonstrates potential as a conservative and adjuvant therapeutic agent for EC, warranting further investigation for fertility preservation.
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