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Objective:To observe the therapeutic effect of electroacupuncture (EA) at Zusanli (ST 36),Guanyuan (CV 4) and Ashi points on adjuvant arthritis rats,and explore the mechanism of EA treatment of rheumatoid arthritis (RA).Methods:Sixty male rats were randomly divided into a normal group,a model group,a methotrexate group and an EA group,with 15 rats in each group.Rats in the normal group and the model group were routinely raised and did not receive treatment;rats in the methotrexate group received methotrexate at a dose of 0.35 mg/(kg·bw),twice a week for 3 weeks;rats in the EA group received acupuncture at Zusanli (ST 36),Guanyuan (CV 4) and Ashi points,and the bilateral Zusanli (ST 36) and Ashi points were connected to EA apparatus,once a day for 3 weeks.The general status,the swelling degree of the toe,the arthritis index (AI) score,the pathological morphology of the ankle joint,and the mRNA expressions of cellular inhibitor of apoptosis protein (c-IAP) 1 and c-IAP2 in joint synovial tissue cells of the rats in each group were observed.Results:The swelling degree of the toe,AI score and mRNA expressions of c-IAP1 and c-IAP2 in the model group were significantly higher than those in the normal group (all P＜0.05).Compared with the model group,the swelling degree of the toe,AI score and mRNA expressions of c-IAP1 and c-IAP2 in the methotrexate group and the EA group improved (P＜0.01 or P＜0.05);the expressions of c-IAP1 mRNA and c-IAP2 mRNA in rat synovial tissues in the EA group were significantly higher than those in the methotrexate group (P＜0.01).Conclusion:EA alleviates joint swelling in rats with adjuvant arthritis.The mechanism may be related to suppressing mRNA expressions of c-IAP1 and c-IAP2,thus to induce apoptosis of synoviocytes.
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Butein is a chalcone, a flavonoid that is widely biosynthesized in plants. Butein has been identified to possess varied pharmacological activity and is extractable from traditional Chinese medicinal herbs, therefore applicable for disease treatment. Recently, in vitro and in vivo studies have shown that butein may induce apoptotic cell death in various human cancer cells. In this study we investigated the apoptotic effect of butein and the underlying mechanisms in human cervical cancer cells. Two cell lines, C-33A and SiHa cells, were treated with butein at different dosages for different durations. The effect of butein on cell viability was assessed by MTT assay, which revealed that butein exerted cytotoxicity in both cervical cancer cells in a dose- and time-dependent fashion. Apoptotic pathway-related factors in the butein-treated cervical cancer cells were then examined. JC-1 flow cytometry, cytochrome c assay, and caspase activity assays demonstrated that butein disturbed mitochondrial transmembrane potential, and increased cytosolic cytochrome c levels and caspase activities in both cervical cancer cells. Western blot analysis revealed that butein downregulated anti-apoptotic protein Bcl-xL and led to proteolytic cleavage of poly (ADP-ribose) polymerase. In addition, butein decreased expressions of the inhibitor of apoptosis (IAP) proteins, including X-linked IAP, survivin, and cellular IAP-1. The findings of this study suggest that butein can decrease cervical cancer cell viability via a pro-apoptotic effect, which involves inhibition of the IAP proteins and activation of both extrinsic and intrinsic pro-apoptotic pathways. Therefore, butein may be applicable for cervical cancer treatment.
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Apoptosis resistance in hepatocellular carcinoma (HCC) is one of the most significant factors for hepatocarcinogenesis and tumor progression, and leads to resistance to conventional chemotherapy. It is well known that inhibitor of apoptosis proteins (IAPs) play key roles in apoptosis resistance, it has become an important target for antitumor therapy. In this study, we examined if melatonin, the main secretory product of the pineal gland, targeted IAPs, leading to the inhibition of apoptosis resistance. To accomplish this, we first observed that four members of IAPs (cIAP-1, cIAP-2, survivin, and XIAP) were overexpressed in human HCC tissue. Interestingly, melatonin significantly inhibited the growth of HepG2 and SMMC-7721 cells and promoted apoptosis along with the downregulation of survivin and XIAP, but had no effect on the expression of cIAP-1 and cIAP-2. These data suggest that the inhibition of survivin and XIAP by melatonin may play an important part in reversing apoptosis resistance. Notably, cIAP-1, survivin and XIAP were significantly associated with the coexpression of COX-2 in human HCC specimens. Melatonin also reduced the expression of COX-2 and inhibited AKT activation in HepG2 and SMMC-7721 cells. Inhibition of COX-2 activity with the selective inhibitor, NS398, and inhibition of AKT activation using the PI3K inhibitor, LY294002, in tumor cells confirmed that melatonin-induced apoptosis was COX-2/PI3K/AKT-dependent, suggesting that the COX-2/PI3K/AKT pathway plays a role in melatonin inhibition of IAPs. Taken together, these results suggest that melatonin overcomes apoptosis resistance by the suppressing survivin and XIAP via the COX-2/PI3K/AKT pathway in HCC cells.