The Effect Of The Cannabinoid Receptor Agonist WIN55,212-2on The Proliferation And Apoptosis Of HepG2and BEL-7402Cells

Cannabinoids have pharmacological effects to chemotherapy-induced vomiting,analgesic, sedative and others. Recently, numerous studies have evidenced the role ofcannabinoids as potential antitumoral drugs owing to their ability to reduce tumor indifferent animal models, including glioma, breast cancer and prostate cancer. But fewresearch has also reported about Hepatocellular carcinoma. We selected thesynthetic cannabinoid WIN55,212-2to study the effect of the activation ofcannabinoid receptor by WIN on the proliferation and apoptosis of hepatoma cells.Purpose:To study the effect of the activation of cannabinoid receptor by WIN on theproliferation and apoptosis of HepG2cells and BEL-7402Cells.Methods:HepG2cells were treated with different doses of the activator of cannabinoidreceptor-WIN, MTT was used to detect the effects of WIN on HepG2cells; DNAladder and flow cytometry (FCM) were used to examine the effects of WIN on theapoptosis of HepG2cells. Cleaved caspase-3and c-myc proteins were determined byWestern blot assay,and caspase-3、8、9activity was measured using a colorimetricmethod.BEL-7402cells were treated with different doses of the activator of cannabinoid receptor-WIN, MTT was used to detect the effects of WIN on BEL-7402cells; DAPIdyeing and flow cytometry (FCM) were used to examine the effects of WIN on theapoptosis of BEL-7402cells. Caspase-3、8、9activity was measured using acolorimetric method. JC-1fluorescent probe was used to measure the effects ofWIN on the mitochondrial membrane potential of BEL-7402cells.Results:WIN could inhibit the proliferation of HepG2cell and induce cell apoptosisdose-dependently. WIN increased cleaved caspase-3protein levels and caspase-3、8、9activity. WIN decreased c-myc protein levels.WIN could inhibit the proliferation of BEL-7402cell and induce cell apoptosisdose-dependently. WIN increased caspase-3、8、9activity. WIN decreased themitochondrial membrane potential.Conclusion:WIN can induce the apoptosis, the effect might be associated with up-regulatingexpression of cleaved caspases-3protein and down-regulating expression of c-mycprotein. The mitochondrion might play an important role in the apoptosis.