Heptachlor Epoxide Enhances Ovarian Cancer Invasion by NF-κB Activation Mediated MMP-2/-9 Expression

Area of Science:

• Environmental toxicology
• Cancer biology
• Molecular mechanisms of carcinogenesis

Background:

• Persistent organochlorine pesticides are endocrine disruptors with potential reproductive health risks.
• Ovarian cancer metastasis remains a significant challenge in women's oncology.
• Heptachlor epoxide is an environmental pollutant of concern for its potential health impacts.

Purpose of the Study:

• To investigate the role of heptachlor epoxide in promoting ovarian cancer invasion and metastasis.
• To elucidate the molecular mechanisms underlying heptachlor epoxide-induced ovarian cancer progression.
• To provide toxicological evidence for assessing environmental pollutant risks in cancer malignancy.

Main Methods:

• In vitro studies using SKOV-3 ovarian cancer cells to assess invasiveness.
• Transcriptomic and molecular biology analyses to identify target genes and pathways.
• In vivo orthotopic ovarian cancer transplantation models in mice.
• NF-κB signaling pathway activation and inhibition studies.

Main Results:

• Heptachlor epoxide dose-dependently enhanced ovarian cancer cell invasion in vitro.
• Heptachlor epoxide upregulated matrix metalloproteinases MMP-2 and MMP-9 expression.
• Heptachlor epoxide activated the NF-κB signaling pathway, leading to p65 nuclear translocation.
• In vivo, heptachlor epoxide exposure increased ovarian cancer metastases in mice, dependent on the NF-κB pathway.

Conclusions:

• Heptachlor epoxide drives ovarian cancer invasion and metastasis via the NF-κB/MMP signaling axis.
• The study provides a complete molecular pathway for heptachlor epoxide's role in ovarian cancer progression.
• Findings offer crucial toxicological insights into the risks posed by environmental pollutants in cancer malignancy.