Figure 6. Single pretreatment of OvCa Cells with an MMP-2/-9 inhibitor or an MMP-2 antibody inhibits peritoneal metastases and increases survival.

(A) Prevention study. SKOV3ip1 cells (1 × 10⁶) were pretreated with MMPI or cyclic peptide and injected i.p. into nude mice. After 28 days, the number of metastasis and tumor weight were determined. **P < 0.001. (B) Intervention study. SKOV3ip1 cells (1 × 10⁶) were injected i.p. into nude mice. After 14 days of tumor growth, mice were treated with the MMPI 3 times per week for 3 weeks. After 28 days mice were sacrificed, the number of metastasis and tumor weight were determined. The columns represent the mean and the bars the SD. *P < 0.01. (C) Prevention study. SKOV3ip1 cells or HeyA8 cells (1 × 10⁶) were pretreated with an MMP-2 antibody or the isotypic specific control antibody and then injected i.p. into nude mice. After 28 days mice were sacrificed, the number of metastasis and tumor weight were determined. **P < 0.001. (D) Survival in prevention and intervention studies. The treatment courses of the prevention and intervention studies were conducted as described above. Mice were sacrificed once they showed signs of distress, and Kaplan-Meier curves were calculated. (E) Tumor lysates from MMPI or control peptide treated mice were subjected to gelatin zymography as described in Figure 1B. (F) Sections of tumors from MMP-2 antibody or mIgG antibody–treated mice were stained with H&E, a Ki-67-specific antibody to detect proliferation, or a CD31-specific antibody to count microvessels. Scale bar: 100 μm.