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