The Photosensitivity Effect Of Fullerene Derivatives On Gastric Cancer Cell SGC-7901

Background and ObjectiveIn recent years, the developing anticancer drugs chemical structureare is very complicated, the complex spatial structure of the drugs resulting in their poor water solubility, also poor of their biocompatibility.These shortcomings greatly reduce the efficacy of anticancer drugs in vivo, even due to the drug non-specific aggregation in some tissues and organs of the organism, which will have some side effects on the organism.Photodynamic therapy is a photosensitizer to produce reactive oxygen species (ROS) in order to kill cancer cells under illumination methods. By taking or photosensitive drug infusion, photosensitizer could priority distribution and retention in tumor tissues, and the light can cause apoptosis of tumor cells, without causing damage to normal cells. For their good pharmaceutical properties, the cancer treatment method is very attractive.Most of the porphyrin photosensitizer are tetrapyrrole-based structure, chlorine, and related molecules. In recent years, the fullerene derivative was found to be very promising photosensitizer, for the fullerene derivative will produce reactive oxygen species after the light treatment, which will have highly efficient on tumors in vitro.Currently the most widely studied fullerene carbon atoms by60by12five-membered rings and20six-membered rings composed of magical football-shaped hollow symmetrical molecules, molecular spherical surface of the body32Using fullerenes alone it is not easy to play a role in the organism in vivo, because of structural features of them. Introducing non-toxic and having the pharmaceutically active groups on fullerenes ball, it can not only improve water-soluble fullerene, but also improve the biocompatibility of fullerene derivatives, at the same time reduce the biological toxicity of fullerenes. Based on the above background, we synthesized fullerene derivatives with photosensitivity, and for the first time we studied the function of a new fullerene derivative against human gastric cancer cells and its mechanism for photosensitivity effects. The study will provide more experimental data for the treatment of cancer by using photosensitive fullerene derivatives.Materials and methods1. Detection of independent roles of4fullerene derivatives in SGC-7901cells by MTT assay.2. Autoxidation of Gallic acid system and methyl violet-Fenton system were used to detect superoxide anion radicals and hydroxyl radicals in the above tumor cells.3.Flow cytometry was used to test the activities (effects on cell cycle, cell biological apoptosis and mitochondrial membrane potential changes) of one of fullerene derivatives B1with different concentration under light and non-light.4. Western blot was performed to detect Bcl-2protein expression in SGC-7901cells under different concentration of fullerene derivatives B1, with light and non-light treatment.Results1. A new fullerene derivative B1had best proliferation inhibition for the SGC-7901cells than fullerene derivative A1, A2and B2. After the sample B1acting on the SGC-7901cells, compared with the same concentration, the light inhibition showed higher significant difference than the non-light group (p<0.05).2. The hydroxyl free radicals produce ability of sample B1was more stronger after light treatment.3. The effect of sample B1on SGC-7901cells in the cell cycle was in a concentration-dependent manner. With the increasing of drug concentration, and under the same drug concentration, the effect of the light group of G2/M phase was more apparent, which showed statistically significant differences (p<0.05).4. Sample B1can promote apoptosis of the tumor cells by lowering the mitochondrial membrane potential.5. Samples B1can decrease Bcl-2protein expression. The higher concentration of samples B1in SGC-7901cells, the lower expression of Bcl-2. In the same concentration of B1, Bcl-2expression of tumor cells decreased significantly after light exposure (p<0.05).Conclusions1. The new synthesized fullerene derivative sample B1had photosensitivity.2. The effects of samples B1on inhibition proliferation and inducing apoptosis of SGC-7901possibly because the drug entered the tumor cells in the light conditions under the cell cycle of G2/M phase and improved the drug radical scavenging ability. At the same time, it reduced the cell mitochondrial membrane potential, resulted in decreased Bcl-2expression in mitochondrial apoptosis pathway, which led to the occurrence of apoptosis in SGC-7901cells.