The Study Of The Productions And The Activities To Tumor Cells Of The Super Micronized Realgar Particles

Arsenic trioxide (As2O3) injectable is the popular chemotheropy medicine to acute promyelocytic leukemia(APL) in clinic. It has been found to down modulate the expression of apoptosis gene bcl-2. Realgar is a kind of mineral Chinese medicine and has been used to treat cancer in 1970s. At that time, the realgar was used in rawish particles and in large dosage, but the therapy effection was weak. Illuminated by the nano-medicine, we transformed the rawish particles into super micronized ones in micron or nanometer. At the same time, the pharmaceutical characteristics were studied. We hope that the realgar particles in micron or nanometer will be an oral chemotherapy medicine in clinics.The realgar were comminuted to be three kinds of particles with different diameters in three ways: water-squelch, airflow, and microjet. Among them, the larger diameters are 10 times of the less ones. The surface characteristics of the realgar particles were studied with scanning electron microscope and X-ray diffraction analysis. It has been shown that they were different in either exterior shape or X-ray diffraction analysis.In vitro, we observed the effections of the three kinds of realgar particles to the proliferation of SMMC7721 cells in several ways: microscope, MTT, DNA agarose gel electrophoresis and flow cytometry(FCM). When the diameters became less, the densities of theSMMC7721 cells went down, the shape of the cells altered more, the DNA prints of the electrophoresis dragged longer, and the rates of S-phase cells became higher. All these showed that the less the diameters of the realgar parcicles were, the stronger the inhibitions were to the SMMC7721 cells.The As concentrations in blood were measured by atomic fluorescent spectrometry before the mice were administrated with realgar agents. It showed that with the degradations of the diameters of the realgar particles, the maximum As concentrations rose, the areas under the curves of concentration-time were enlarged, and the other pharmacokinetical parameters altered , too. At the same time, the serum of the mice which had been administrated with the realgar of the least diameter could inhibit the growth of the SMMC7721 cells at the highest level.The cells of the Hep ascites tumor mouse were transplanted under the skin of ICR mice to form tumors, then the ICR mice were administrated with the realgar agents once a day for 10 days. We found that the realgar could make the transplanted tumors shrink, and the necrosis areas become larger. And the less the diameter of the realgar particles was, the more obvious the effections were.