R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of National Academy of Sciences, Kyiv, Ukraine
Abstract. Aim: to reveal the differences in the production of vascular endothelial growth factor (VEGF) by Lewis lung carcinoma (LLC) and its cisplatin-resistant variant (LLC/R9) and to study the biological correlates between these differences and metastasis. Results:in vitro investigations showed that in the absence of cisplatin treatment cisplatin-resistant LLC/R9 cells produced increased level of VEGF in comparison with parental cells. The treatment of LLC/R9 cells with cisplatin in relatively low concentrations resulted in the decreased level of VEGF production. Meanwhile the same concentrations of cisplatin enhanced VEGF production by LLC cells. In vivo the dynamics of serum VEGF level in LLC-bearing mice was found to differ from that in mice with LLC/R9 by lower level of VEGF and by the existence of an essential lag time in the production of this factor. Unlike LLC, the dynamics of serum VEGF level in LLC/R9- bearing mice was characterized by absence of time delay and an increased level of VEGF. It has been shown that such differences in circulating VEGF are accompanied by the distinction in metastatic lung injury. The volume of lung metastases in mice with LLC/R9 was considerably higher than that in the animals with LLC, although the maximum number of lung metastases in animals with resistant tumor was by 22% less than in mice with parental one. Conclusion: Revealed changes in the secretion of VEGF give ground to suggest that intracellular mechanisms, providing increased production of VEGF by Lewis lung carcinoma cells in response to cisplatin action, are part of the adaptive reactions of tumor cell and underlie the formation of drug resistance of malignant tumors.
Key Words: VEGF, drug resistance, metastasis, cisplatin, Lewis lung carcinoma.
