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Published on: August 2, 2024
The inhibitory effect of doxycycline on cisplatin-sensitive and -resistant epithelial ovarian cancer
1Department of Gynecology and Obstetrics, Changhai Hospital, Second Military Medical University, Shanghai, P.R.China; Department of Physiology, Second Military Medical University, Shanghai, P.R.China.
Background:
Detecting a new effective and hypotoxic anticancer drug is an emerging new strategy for cancer chemotherapy. Doxycycline (DC) is a kind of antibiotics but also inhibits tumorigenesis.
Methods:
MTT and cell invasion assay, flow cytometry, western-blot analysis and nude mice were used to investigate the effects and underlying mechanisms of doxycycline on epithelial ovarian cancer cells.
Results:
Doxycycline inhibited the proliferation and invasion of SKOV3 and SKOV3/DDP; induced moderate apoptosis of SKOV3/DDP. CXCR4 expression at both mRNA and protein levels was downregulated in both cell lines when treated with doxycycline. Akt and ERK1/2 were involved in doxycycline effect on cell proliferation of SKOV3 but not of SKOV3/DDP. Akt and EKR1/2 phosphorylation were activated by SDF-1α, which was then inhibited by doxycycline in SKOV3. Pro-caspase-3 expression was significantly higher in SKOV3 than that in SKOV3/DDP which was upregulated when treated with doxycycline. In vivo, doxycycline inhibited peritoneal tumor xenograft and decreased malignant ascites.
Conclusion:
Doxycycline not only has an inhibitory effect on ovarian cancer, but also can increase sensitivity to cisplatin. SDF-1α/CXCR4-regulated Akt and ERK 1/2 activations are probably involved in the antitumor effect of doxycycline on SKOV3 cells, while upregulation of pro-caspase-3 may be the main mechanism involved in SKOV3/DDP cells.
Insights
Doxycycline, an antibiotic, shows promise in treating ovarian cancer by inhibiting tumor growth and invasion. It may also enhance cisplatin sensitivity, offering a new therapeutic strategy.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- The search for novel, less toxic anticancer drugs is crucial for effective cancer chemotherapy.
- Doxycycline, an antibiotic, exhibits potential anti-tumorigenic properties.
Purpose of the Study:
- To investigate the anti-cancer effects of doxycycline on epithelial ovarian cancer cells.
- To elucidate the underlying mechanisms of doxycycline's action in ovarian cancer.
Main Methods:
- Cell proliferation and invasion assays (MTT, cell invasion assay).
- Flow cytometry and western-blot analysis for molecular mechanism investigation.
- In vivo studies using nude mice xenograft models.
Main Results:
- Doxycycline suppressed proliferation and invasion in SKOV3 and SKOV3/DDP ovarian cancer cells.
- Downregulation of CXCR4, Akt, and ERK1/2 phosphorylation observed, with variations between cell lines.
- In vivo, doxycycline reduced tumor xenograft growth and ascites in mice.
Conclusions:
- Doxycycline demonstrates inhibitory effects on ovarian cancer and enhances cisplatin sensitivity.
- The SDF-1α/CXCR4 pathway and associated signaling (Akt, ERK1/2) are implicated in doxycycline's effects.
- Upregulation of pro-caspase-3 may be a key mechanism in cisplatin-resistant cells.
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