Experimental study of enhanced cytotoxicity of Navelbine to human pulmonary carcinoma cells A549 with hyperthermia

Objective:To investigate the effect and mechanism of hyperthermia on sensitivity of Navelbine. Methods: The working concentrations of NVB against human pulmonary adenocarcinoma cells(A549) were determined by MTT assay that has been developed for quantitative evaluation of the proliferation of cells. Then hyperthermia and chemotherapy were used singly or concurrently and the cell survival rates were obtained at 24h. The anticancer effect was evaluated by Veleriote method. The changes in cell cycle of cells and the assessment of apoptosis rates after treated for 42℃ hyperthermia and NVB were analysed by flow cytometry (FCM). Results: The concentration was defined as that of IC10-IC20 at 24h. It turned out to be 10ug/ml. Both single 42℃ hyperthermia and single chemotherapy suppressed the proliferation of A549 cells(P0.05); Combination of 42℃ hyperthermia and chemotherapy suppressed proliferation and killed more cells than single chemotherapy and single hyperthermia(P0.01).Flow cytometry showed that 42℃ hyperthermia resulted in progressive decrease in cells in S phase; Single chemical drug arrested cell cycle progression in G2/M phase; Compared with the group of single chemotherapy, the proportion of S phase cells of the group of combined treatment of 42℃ hyperthermia and chemotherapy decreased while the proportions of G2/M phase cells increased. The apoptosis rates of the four groups (control group, hyperthermia group, chemotherapy group and combination group)were 1.5%,7.9%,13.9% and 29.1% respectively. Conclusion: 42℃ hyperthermia can obviously enhance the cytotoxicity of NVB; The anti-tumor mechanism may be related to disturbance of cell cycle.