Effects of combining Taxol and SC-560 on angiogenesis of ovarian cancer <em>in vivo</em> — ASN Events

Effects of combining Taxol and SC-560 on angiogenesis of ovarian cancer in vivo (#221)

Wei Li 1 , Liang Wan 1 , Ling Yun Zhai
  1. Department of Gynecology, Nanjing Medical University of Hangzhou Hospital, Hangzhou, Zhejiang, China

Background Taxol is known as a front-line agent for ovarian cancer chemotherapy; however, long-term treatment often results in chemoresistance. Over-expression of cyclooxygenase (COX)-1 is associated with elevated levels of angiogenic factors in ovarian carcinoma, which was inhibited by COX-1 selective inhibitors.
Aim To evaluate the effects of SC-560, a COX-1 inhibitor, administered in combination with taxol on angio-genesis of the antitumor efficacy in a human ovarian SKOV-3 carcinoma cell xenograft-bearing mice model.
Methods The experiments were continued for 28 days. Animals were treated with 3 mg/kg SC-560 alone, 100 mg/kg celecoxib (a COX-2-selective inhibitor) alone by gavage twice a day, 20 mg/kg Taxol alone intraperitoneally once a week or in combination with SC-560 or celecoxib for three weeks. To test the antiangiogenic mechanism of the combination treatment, the mRNA levels of vascular endothelial growth factor (VEGF) in tumor tissues was determined by reverse transcription-polymerase chain reaction (RT-PCR). The Microvessel density (MVD) of ovarian carcinomaxenografts was determined by immunohisto-chemistry with anti- CD34 as the label.

Results  Mean tumor volume in SC-560/ taxol group was first significantly lower than control at day 14 (p <0.05). On day 7 after the end of administration, tumor volume in the combination group was reduced by 55.35% compared with control mice, which is significant statistically compared with that of control group (p <0.05). The MVD value in the SC-560/Taxol group were notably inhibited compared with the Taxol group (p<0.001). Moreover, the VEGF mRNA levels and MVD value in the SC-560/Taxol group were significantly different from the celecoxib/Taxol group (p <0.05, p <0.05 and p <0.001, respectively).
Conclusions The present study demonstrated that synergism between Taxol and SC-560 combination treatment has particular potential for chemoprevention of ovarian cancer growth, and that SC-560 enhances the anti-angiogenic effects of Taxol and these effects are better than with celecoxib.

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