Interleukin-8-specific miRNA for the treatment of ovarian cancer
Scientists at the University of Texas, working under the guidance of Professor Anil Sood, have demonstrated that a high level of interleukin-8 (IL-8) expression in malignant ovarian tumors is associated with late stages of the tumor process and early death of patients. The results of laboratory experiments and experiments on a mouse model of the disease have shown that miRNA can be used to suppress the synthesis of IL-8 and reduce the size of tumors by worsening their blood supply.
Ovarian cancer is often diagnosed at late stages. Treatment usually consists of surgical removal of the tumor and subsequent chemotherapy. This allows you to suspend the development of the disease for a while, but in most cases the tumor recurs, which leads to a fatal outcome.
To assess the role of IL-8 in the development of ovarian cancer, the authors analyzed the tumors of 102 patients treated for this disease in the period from 1988 to 2006. Tumors of 43 patients had a high level of IL-8 expression, and 59 had a low level. The average survival of patients with high levels of IL-8 in tumors was 1.62 years, and patients with low levels of this protein – 3.79 years.
All tumors with a high level of IL-8 were characterized by a high degree of malignancy, 42 out of 43 tumors of this group were at stage III or IV at the time of diagnosis. For comparison, 10 out of 59 tumors with low IL-8 expression were in the early stages of progression, and 6 were characterized by a low degree of malignancy.
Scientists packed miRNAs selectively blocking the synthesis of IL-8 inside liposomes – tiny droplets of fat that have the ability to penetrate deep into tissues and ensure the delivery of miRNA inside tumors. The introduction of such liposomes reduced the size of tumors that developed in the body of mice from two lines of malignant cells by 32% and 52% compared with control animals receiving injections of control miRNAs (without liposomes) or empty liposomes.
Mice treated with a combination of IL-8-specific miRNAs and the chemotherapy drug docetaxel had a decrease in tumor mass by 90% and 98% for two cell lines. With the introduction of control miRNAs and docetaxel, the corresponding indicators were 67% and 84%.
After that, the authors tested the effectiveness of the therapeutic approach on mice injected with an ovarian cancer cell line resistant to taxane-based drugs, to which docetaxel belongs. At the same time, injections of only the liposomal form of miRNA reduced the size of tumors by 47%, and additional administration of docetaxel increased this figure to 77%, which indicates the return of tumor sensitivity to drugs of this group.
The scientists evaluated the effect of IL-8-specific miRNA on the blood supply of tumors by measuring the density of the tumor vascular network. The introduction of liposomes containing miRNA reduced the density of blood vessels in tumors formed by two types of cancer cells by 34% and 39%.
The authors consider the results to be very encouraging and plan to conduct clinical trials of the treatment method they have developed. In addition, they believe that miRNAs specific to IL-8 expressed by many types of tumors can be used to treat other forms of cancer. Currently, work is already underway to study the role of IL-8 in the progression of melanoma.
Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily
03.03.2008