Aspirin and Cervical Cancer

Cervical cancer is caused by a human papilloma virus and is associated with elevated expression of COX-1 and COX-2, which in turn induce the formation of several prostaglandins (PGs). Over-expression of COX-2, in particular, said Dr Jabbour, induces malignant change in epithelial cells by inhibiting their instruction to commit suicide (apoptosis). Dr Jabbour and his colleagues studied expression of COX and PGE2 synthesis and signalling in cultures of tissues taken from patients with cervical cancer (explants).

All the cancer cells in the explants, but none of the normal cervix cells, showed elevated levels of COX-1 and COX-2. High levels of COX-2 activity were also found in the epithelial cells lining the blood vessels, and there was also persistent upregulation of EP2 and EP4 receptors in the cancer specimens. Increased activity of EP2 and EP4 are also a sign of increased prostaglandin expression. This was a big difference between cervical carcinoma and normal cervix cells that was lessened when the cells were exposed to indomethacin, showing that the difference was the result of COX activity.

Tumours depend on the formation of new blood vessels around them (angiogenesis) for their growth. Dr Jabbour's group showed that COX-1 produces increased activity in angiogenic factors in epithelial cells from blood vessels of cervical cancer patients. Production of anti-angiogenic factors is blocked - in effect a double effect promoting new blood vessel development.

Prostaglandin E is found in very high levels in semen. When seminal plasma was added to cervical epithelial cells, there was a huge upregulation in COX-2, and in the expression of surface receptors EP1, 2, 3 and 4. All of these changes promote tumour growth and spread. Adding indomethacin or aspirin to the culture ensures that this upregulation does not happen.

Professor Jabbour raised the question of whether EP receptor antagonist therapy might be the way forward for the prevention of the growth and spread of tumours in sexually active women.

Professor McVie asked Professor Jabbour what might be the purpose of having PGs in semen? He replied that it may be a form of immune suppression to stop the sperm being killed as a foreign body. The semen 'delivers an immune suppression blanket'. aspirin will have a protective effect by reducing receptor numbers and activity. The woman, not the man, should take the aspirin.

Professor Anthony Howell, Professor of Medical Oncology at the University of Manchester and at the Christie Hospital Cancer Centre in Manchester, continued the Aspirin and Cancer theme with a review of breast cancer research results.