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Anlotinib Suppressed Ovarian Cancer Progression via Inducing G2/M Phase Arrest and Apoptosis
Yanghui Zhu1, Xiaoyu Wang1, Zhaoyang Chen1
1Department of Pharmacy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
Abstract:
Ovarian cancer remains the most common gynecologic malignancy, because of its chemotherapy resistance and relapse. Anlotinib, a new oral multi-targeted tyrosine kinase inhibitor, has shown encouraging antitumor activity in several preclinical and clinical trials, while its effect on ovarian cancer has not been reported. In this study, we investigated the antitumor activity and underlying mechanism of anlotinib in ovarian cancer. Cell viability was analyzed by Cell Counting Kit-8 assay. Migration was measured by wound-healing assay. The cell cycle distribution and cell apoptosis rate were detected by flow cytometry. In vivo antitumor effect was analyzed in mouse ovarian carcinoma peritoneal metastasis model. We found that anlotinib inhibited the proliferation of ovarian cancer cells in a dose- and time- dependent manner by inducing G2/M phase arrest and apoptosis. Moreover, anlotinib upregulated the the phosphorylation of Histone H3, and expression of p21 protein in vitro. In addition, anlotinib inhibited the migration of ovarian cancer cells in vitro. Furthermore, anlotinib inhibited tumor growth by inhibiting cell proliferation and suppressing ovarian cancer angiogenesis in vivo. This study demonstrated the extraordinary anti-ovarian cancer effect of anlotinib, which may provide a promising therapeutic strategy for ovarian cancer.
Insights
Anlotinib, a multi-targeted tyrosine kinase inhibitor, effectively inhibits ovarian cancer cell proliferation and migration. This drug induces cell cycle arrest and apoptosis, offering a promising new therapeutic strategy for ovarian cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Ovarian cancer is a leading gynecologic malignancy with significant challenges due to chemotherapy resistance and relapse.
- Anlotinib, an oral multi-targeted tyrosine kinase inhibitor, has demonstrated antitumor activity in various cancers, but its efficacy in ovarian cancer was previously unreported.
Purpose of the Study:
- To investigate the antitumor activity of anlotinib in ovarian cancer.
- To elucidate the underlying mechanisms of anlotinib's action in ovarian cancer cells and in vivo models.
Main Methods:
- In vitro: Cell Counting Kit-8 assay for viability, wound-healing assay for migration, and flow cytometry for cell cycle and apoptosis.
- In vivo: Mouse ovarian carcinoma peritoneal metastasis model to assess antitumor effects.
Main Results:
- Anlotinib significantly inhibited ovarian cancer cell proliferation and migration in a dose- and time-dependent manner.
- The drug induced G2/M phase cell cycle arrest and apoptosis, upregulated Histone H3 phosphorylation and p21 expression in vitro.
- Anlotinib suppressed tumor growth, proliferation, and angiogenesis in a preclinical ovarian cancer metastasis model.
Conclusions:
- Anlotinib exhibits potent anti-ovarian cancer effects by inhibiting proliferation, migration, and angiogenesis.
- The findings suggest anlotinib holds promise as a novel therapeutic strategy for treating ovarian cancer.
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