Sea Cucumber Reduces Breast Cancer Tumor Size Through Inhibition of MMP9 Dependent HER2 Expression in Breast Cancer Mice Model
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Abstract
Breast cancer is one of the most common types of cancer affecting Indonesian women, with more than 80% of cases being found at an advanced stage with distant metastases. HER2- positive breast cancer is an aggressive subtype of metastatic breast cancer. HER2 is an oncogene responsible for cell growth but also associated with tumor invasion by activating the MMP9 promoter. This study aims to determine the role of sea cucumber Holothuria scabra methanol extract (HSE) in reducing tumor size by inhibiting HER2 and MMP9 overexpression in a breast cancer mice model. Thirty female C57BL6 mice were divided into five groups (n=6), NC (negative control), PC (positive control/breast cancer mice model), and T1, T2, and T3 as treatment groups. The PC, T1, T2, and T3 were given a high-fat diet and DMBA 1 mg/kgBW by subcutaneous injection. Administration of HSE 0.33, 0.66, and 0.99 g/kgBW for 12 weeks to the treatment groups. The results showed a highly significant difference in tumor size between PC compared to T1, T2, and T3 groups (p<0.001), the tumor size reduced in a dose-dependent manner by 25.98%, 32.83%, and 43.30% compared to the PC group. Administration of HSE 0.66 and 0.99 g/kgBW significantly decreased HER2 and MMP9 expression, and there is a positive high correlation (R2=0.7707) between HER2 and MMP9 expression. It can be concluded that the administration of HSE decreases the overexpression of HER2 and MMP9. Therefore, it can be used as a therapeutic candidate against breast cancer. The MMP9 expression partly depends on HER2 activity.
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