SipA decreases a molecule associated with tumor drug resistance
A study, led by researchers at the University of Massachusetts Medical School, suggests a possible way to treat drug-resistant cancers with traditional drugs. The researchers have discovered that Salmonella invasion protein A (SipA), which is a protein of Salmonella bacteria, decreases a molecule responsible for drug resistance in various cancer types. Moreover, they have also developed an approach for delivering SipA to tumors. Experiments in mouse models of colon and breast cancers have demonstrated that this approach is effective in reducing tumors.
For many years, it has been found that certain bacteria can inhibit tumors. Recent studies have suggested the possibility of using bacteria like Salmonella to boost the immune response against cancer. Some species of bacteria are able to selectively grow in tumors. However, the underlying mechanisms are still unknown. A major author of the new study, Dr. Beth A. McCormick, was investigating the effect of SipA on some transport proteins of human cells, one of which is called P-gp transporter protein. She discovered that the bacterial protein seems to fully remove P-gp.
Since P-gp is an important protein on the cell surface that pumps foreign substances out of the cell, Dr. McCormick suggested that blocking P-gp may help Salmonella bacteria to infect cells. When the cancer returns, excessive P-gp in cancer cells may cause drug resistance, because the protein can remove drugs out of cells. The novel study indicated that SipA could eliminate P-gp.
The SipA protein is very unstable outside of the bacterial cell. Because of this, the McCormick and colleagues wanted to develop a method that can stabilize and deliver the protein. They used a gold nanoparticle scaffold, which they described as a nanobug, to mimic the Salmonella bacteria. The researchers tested a combination of the SipA-nanobug and Doxorubicin (a common cancer therapy) in mouse models of colon and breast cancers. Tumors in these mice became almost undetectable after 30 days. Based on the significant results, the team plans to further explore the therapeutic potential of SipA.