Intratumoral injection of arsenic to enhance antitumor efficacy in human esophageal carcinoma cell xenografts

Abstract

To enhance the therapeutic efficacy of anticancer agents and to reduce systemic side effects, it was decided to study the effect of arsenic trioxide directly on solid tumors to observe the anticancer effect of arsenic on tumors and the distribution of arsenic in tumors and other organs. Esophageal carcinoma cells were heterotransplanted in severe combined immunodeficient (SCID) mice in both laterals of the abdominal wall. When both lateral tumors had grown to approximately 10x8x5 mm3, tumor-bearing mice were used for 2 experiments. The right tumors were treated with intratumoral injection of As2O3 in 1, 5 and 10 micro g per day for 10 days sequent. The left tumors were treated with phosphate buffer solution as controls. To explore the distribution of As2O3 remaining in tumor and some organs, a single intratumoral injection of As2O3 was studied with quantitative measurement of arsenic by means of atomic absorption spectrometry. The results revealed that on the 17th day after the 1st injection As2O3-treated tumors were suppressed markedly compared to that of the contrarily lateral tumor accompanied by marked apoptosis and necrosis in tumor cells. The tumor growth inhibition (TGI) was 13.56, 62.37 and 76.92% in 1, 5 and 10 micro g group, respectively. There were no pathological changes in heart, lung, spleen, liver, kidney or brain after arsenic administration. Distribution of As2O3 revealed that As2O3 remained at higher concentration in arsenic-treated tumor tissue than in other organs. Our data suggest that intratumoral delivery of As2O3 efficiently suppresses growth of transplanted esophageal carcinoma without systemic side effects. The protocol of As2O3 intratumoral injection will be its potential clinical utility for therapy of solid tumors.