The Inhibitory Effect Of Botulinum Toxin Type A On Gastric Cancer Cells In Vitro

Background:Gastric cancer is the most common malignant tumor in digestive system. The incidence of gastric cancer ranks the second in China, just behind lung cancer. For patients with advanced gastric cancer who can’t accept surgery treatment, chemotherapy and targeted therapy has made great progress. But the overall effect is not satisfied, and the 5 year survival rate in some area still remains below 20%. More effective therapeutic technique is required to improve the therapeutic effcect of advanced gastric cancer. Botulinum toxin type A (BTX-A), a neurotoxin which is produced by Clostridium botulinum, has been widely used in cosmetic field and muscle spasm diseases. BTX-A was reported to inhibit prostate cancer and breast cancer cells recently, and it also could surpress gastric cancer through denervation in mice. However, whether BTX-A has a direct inhibitory effect on gastric cancer cells and its mechanism are still blank.Objective:This article intends to study the effects of BTX-A on the proliferation and migration ability of gastric cancer cell lines, and to explore inhibitory effcet of BTX-A on gastric cancer cells. In order to provide a new technique for the treatment of gastric cancer.Methods:Two gastric cancer cell lines (BGC-823 and MGC-803) were involved in this study. MTT assays and colony formation were employed to evaluate the effect of BTX-A on cell proliferation in BGC-823 and MGC-803 cells,and wound healing assays was used to evaluate the effect of BTX-A on cell migration in BGC-823 and MGC-803 cells.Results: ① The growth of BGC-823 and MGC-803 cells was inhibited by BTX-A treatment with the concentration of 0.25IU/ml,0.5 IU/ml and 1 IU/ml, respectively. The efficiency of inhibition was increased with the elevation of BTX-A concentration and the inhibitory effect of 1 IU/ml BTX-A on BGC-823 and MGC-803 cell lines was the most obvious.The optical density of the 1 IU/ml BTX-A group and control group in BGC-823 and MGC-803 cells were 0.54±0.02 vs.0.62 ±0.01、0.50±0.01 vs.0.56± 0.02 (p<0.05)② The prolification was inhibited under 1 IU/ml of BTX-A concentration, and the effect of inhibition was enhanced with the increasing treatment time in 0,24,48,72,96 hours, respectively. In 72h, the optical density of the 1 IU/ml BTX-A group and control group in BGC-823 and MGC-803 cells were 0.46±0.03 vs.0.52±0.03、0.59±0.01 vs.0.66±0.02 (p<0.05). In 96h, the optical density of the 1 IU/ml BTX-A group and control group in BGC-823 and MGC-803 cells were 0.47±0.04 vs.0.56±0.05、0.62± 0.01 vs.0.69±0.01 (p<0.05)③ Colony formation showed that BTX-A could inhibit the prolification of BGC-823 and MGC-803 cells. The colony numbers of BGC-823 and MGC-803 cells were 229.33±17.99 vs.297.33±19.69、77.33±9.98 vs.157.33±16.11 with and without BTX-A after 14 days (p<0.05)④ The wound healing assays showed that the migration of BGC-823 and MGC-803 cells was inhibited apparently by BTX-A. The wound width of BGC-823 and MGC-803 cells with and without BTX-A in 72h were 15.87±0.57 vs.8.30±0.75、 15.87±1.18 vs.9.17±1.86 (p<0.05)Conclusion:The proliferation and migration of BGC-823 and MGC-803 cells were inhibited significantly by BTX-A. The inhibitory efficiency was increased with the increasing concentration and time course of treatment.