According to a new research, two correlated enzymes would be targeted for treating lung cancer. The researchers said so after blocking the production of the two enzymes in transgenic mice. This blocking caused inhibition of cell growth, fewer tumors and improved survival rate in mice. The research was carried out by researchers at the Sahlgrenska Academy at the University of Gothenburg, Sweden. It was published in the journal Proceedings of the National Academy of Sciences (PNAS).
It is a fact that several types of cancer along with the growth and spread of tumors are controlled and stimulated by Ras and Rho proteins. In order to function, these proteins require modification carried out by two related enzymes, FT and GGT. As a result, various pharmaceutical companies produced compounds that lower the activity of these two enzymes aiming to block the function of Ras and Rho proteins and resulting in hindering the course of the disease.
However, using treatment with various substances in order to block these two enzymes has been usually non-specific, and the efficacy of these compounds showed wide variation. That resulted in difficulty for researchers to evaluate the potentials of these enzymes to be targeted for medicines. "We therefore developed genetic strategies in mice, known as transgenic mice, to switch off the genes coding for FT and GGT, enabling us to investigate whether a complete blockade of FT or GGT can inhibit the development of lung cancer, and whether this has side-effects in the lungs," said researcher Anna-Karin Sjögren, who led the study along with Meng Liu, both from the Department of Clinical and Molecular Medicine.
The researchers used transgenic mice with mutated Ras protein responsible for lung cancer. Then researchers stopped the production of FT or GGT in these mice's lungs, this was carried out by switching off the relevant genes. Liu explained "When we turned off the FT gene, the mice developed fewer lung tumors and lived longer," he added "At cellular level, the blockade of FT meant that the tumour cells were no longer able to divide. When we blocked the production of GGT, we saw the same effects: inhibition of cell growth, fewer lung tumors and improved survival."
When switching off both genes at the same time, there was a significant drop in the number of lung tumors and thus the mice lived much longer. The researchers concluded also that the blocking these two enzymes did not cause any side-effects to the lungs. Moreover, lung tumor cells showed more sensitivity to the treatment rather than normal lung cells. The researchers concluded "Our findings show that FT and GGT are promising targets for the treatment of lung cancer," they added "The next step in our research is to find out whether blocking these enzymes can have side-effects in other tissues."