Basic and clinical study of increased effect of partial anti-tumor agents by infusing sodium bicarbonate through target artery

Abstract

Objective

To observe the influence of pH value on the proliferation of LAK cells and on the killing effect of rIL-2, IFN-α2b, TNF-α, LAK cells and doxorubicin on malignant tumor cells, and investigate the possibility of increasing the efficacy of rIL-2 or IFN-α2b and doxorubicin by infusing sodium bicarbonate (NaHCO₃) through target arteries.

Methods

Separating single nucleus cells from peripheral blood of healthy men, and observing the influence of pH on the activation of single nucleus cells by rIL-2. MTT assay was used to measure the killing effect of rIL-2, IFN-α2b and TNF-α on 7404 cells and the increased effect of doxorubicin on rIL-2 and IFN-α2b, the cytotoxity of LAK cells in different pH. Forty-two patients with advanced primary liver cancer were obtained by stratified random, NaHCO₃, rIL-2/IFN-α2b and doxorubicin were infused through target arteries. The efficacy was estimated after two cycles.

Results

The conditions of pH 7.3 and pH 7.6 in vitro helped the proliferation of LAK cells and the killing effect of rIL-2, IFN-α2b and LAK cells on 7404 cells. In the condition of pH 6.8 there was almost no killing effect for LAK cells. In the condition of pH 7.0, 7.2, 7.4 and 7.6, the killing rate of TNF-α to 7404 cells increased by degrees, and in pH 7.4 the killing effect was the optimum. After two cycles treatments in the 42 patients with advanced primary liver cancer, the response rate (CR+PR) was 88% (37/42). The median overall response and median overall survival were increased, and no complication associated with infusing sodium bicarbonate was observed.

Conclusion

The killing effect of rIL-2, IFN-α2b, TNF-α and doxorubicin on malignant tumor cells was enhanced by increasing the pH value.