LOS ANGELES--Although a number of new angiogenesis inhibitors are
under development, researchers reported at an ASCO poster session
that an established anticancer agent may also have antiangiogenesis
Derick H. Lau, MD, PhD, and his colleagues at the University of
California, Davis, found that paclitaxel (Taxol) is able to block
angiogenesis and that this function is independent of the drugs
antiproliferative properties. This suggests that paclitaxel might
help prevent metastasis by blocking the growth of new blood vessels
needed by growing tumors.
Dr. Lau and his associates studied the angiogenesis effect by
implanting a highly vascularized murine breast carcinoma into nude
mice. "This is a good model for metastatic human disease,"
Dr. Lau said. "In these animals, 90% of tumors will metastasize
to the lung in 50 days."
Paclitaxel, at doses of 0, 3, and 6 mg/kg/d, was administered
intraperitoneally for 5 days to three groups of four animals per
group. Tumor growth was measured every 2 days. Eight days after the
last dose of paclitaxel, microcirculation of the tumor was studied
with computer-assisted intravital microscopy. Microvessel density was
determined with alpha-actin immunostaining under light microscopy.
The implanted tumors grew at the same rate in all groups, with a
doubling time of 7 days in each group (P > .05). However, Dr. Lau
reported that the intratumoral tortuosity index of the
microcirculation was significantly reduced in the paclitaxel-treated
animals, compared with controls (P < .05). Similarly, the animals
treated with paclitaxel had microvessel density significantly lower
Vessel density decreased in a dose-related manner: From 33 per
high-power microscopic field with no paclitaxel, to 17 with a 3 mg/kg
dose, to 11 with a 6 mg/kg dose (P < .05).
"We conclude that paclitaxel possesses an antiangiogenesis
property in breast cancer independent of its antiproliferative
action," Dr. Lau said. "The next step will be to see if by
decreasing microvascular density, we can decrease metastasis."