西亚试剂：PKG can reduce vascular endothelial growth factor

发布时间：2025-09-12

He’s already shown that PKG can reduce vascular endothelial growth factor, or VEGF; anti-VEGF drugs are the focus of numerous anti-cancer trials underway in the country because of VEGF’s critical role in development of new blood vessels. “Maybe by activating PKG or increasing PKG expression in tumors, we are going to reduce the amount of VEGF they produce,” he says. “We don’t know whether PKG has a role in going from normal tissue to the initiation of a tumor, but we think it’s important to the tumor both in terms of angiogenesis and blocking metastasis.” He points to one of his studies in which colon cancer’s spread to the lungs – a common path for metastatic colon cancer – was completely blocked by PKG expression.

A big part of the magic of PKG may be its impact on a gene called beta-catenin, which enables many stem cells, including those in the skin, bone marrow and colon, to proliferate throughout life. Little pits called crypts in the wall of the colon contain Wnt hormone which stimulate nearby stem cells, causing an increase in beta-catenin. The net effect is the colon makes new cells to replace cells lost to the ongoing grind of absorbing water and minerals from food and forming and eliminating waste.

As cells start moving out of the crypt, away from the Wnt hormone, beta-catenin levels go down so cells should stop dividing and start maturing. Essentially all colon cancers have an aberration in this beta-catenin system that prevents normal degradation and allows cell to keep proliferating.

“In the normal cells that line the colon, you don’t see very much beta-catenin. We think PKG in these cells keeps it that way to keep the cells from continuing to proliferate and spread,” says Dr. Browning, who has already shown that in the test tube at least, adding PKG lowers beta-catenin levels. Interestingly, beta-catenin also is known to regulate VEGF expression in colon cancer.

“In a nutshell, the first and most important genetic lesions leading to colon cancer cause increased beta-catenin levels,” says Dr. Browning. “We found PKG can knock down beta-catenin levels by up to 80 percent in some colon cancer cells and we think that is part of the mechanism by which PKG is able to block tumor angiogenesis and metastasis.”

He’s excited by the implications and is involved in extensive collaborations to understand how PKG regulates beta-catenin and how it might be used in cancer therapies.

Evidence of PKG’s effectiveness in fighting colon cancer in humans may already be available. Colon and rectal cancer is the third most common cancer in men and women in the United States but it’s rare in developing countries where residents eat less processed food and ingest more bacteria. Some of these bacteria make a protein, STa, which appears to prevent and even kill colon cancer cells. Dr. Browning believes that PKG is responsible for STa’s anti-cancer effects.

Source: Medical College of Georgia

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