Endostatin, radiation therapy combination stops blood vessel growth in mice

Researchers report that in laboratory animals, the combination of radiation and the anti-angiogenic drug, endostatin, appears to work synergistically together to stop development of new blood vessels that seek to grow and nourish damaged tumors.

Researchers at The University of Texas M. D. Anderson Cancer Center found that the regrowth of new blood vessels was reduced five-fold in mice with implanted squamous cell cancer treated with radiation and endostatin compared to diseased mice that had radiation or endostatin alone, says Satoshi Itasaka, M.D., a visiting postdoctoral fellow from Kyoto, Japan.

“Endostatin enhanced the anti-tumor effects of irradiation and 40 percent of mice in the combined treatment group achieved long-term survival and tumor control,” says Itasaka.

The researchers then examined the tumors and found that expression of crucial proteins varied among the treatment groups. Specifically, a “sharp” increase in VEGF/VPF, IL-8 and MMP2 proteins were found in tumors that had been irradiated. These proteins are proangiogenic and invasive factors that are needed to “signal” blood vessels to grow to tumor cells, to nourish them. Radiation increased levels of these proteins, but then endostatin “blocked” them from acting.

“After radiation, there is a regrowth of blood vessels as well as tumor cells, and endostatin seems to work to stop blood vessel regrowth,” says Itasaka. “Why the combination of irradiation and endostatin works well is not fully understood yet, but it appears they may overcome the limitations of each other.”

Other studies have looked at the effect of a combination of radiation and anti-angiogenesis drugs on death of blood vessel cells, but this is the first to examine whether these blood vessel cells regrow after irradiation, and what effect endostatin has on that regrowth, he says.