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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. 相似文献
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Very brief physician advice and supplemental proactive telephone calls to promote smoking reduction and cessation in Chinese male smokers with no intention to quit: a randomized trial 下载免费PDF全文
Lei Wu Yao He Bin Jiang Di Zhang Hui Tian Fang Zuo Tai Hing Lam 《Addiction (Abingdon, England)》2017,112(11):2032-2040
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Real‐world effectiveness and safety of paritaprevir/ritonavir,ombitasvir, and dasabuvir with or without ribavirin for patients with chronic hepatitis C virus genotype 1b infection in Taiwan 下载免费PDF全文
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Effectiveness of systematic training in the application of narrow‐band imaging international colorectal endoscopic (NICE) classification for optical diagnosis of colorectal polyps: Experience from a single center in China 下载免费PDF全文
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