Anesthetic effects of isoflurane and the molecular mechanism underlying isoflurane-inhibited aggressiveness of hepatic carcinoma

摘要

Anesthesia is produced by drugs or other methods, and refers to the attenuation of pain via reversible suppression of neuronal transmission in the central and peripheral nervous systems, during surgery. Clinical investigations have indicated that the anesthetic action of isoflurane is efficient to alleviate pain during tumor resection clinical trials. In addition, it has been reported that isoflurane can induce caspase-3 activation and is associated with apoptosis of tumor cells. The present study investigated the anesthetic effects and molecular mechanisms underlying isoflurane-induced apoptosis in patients with hepatic carcinoma. Furthermore, the pain of patients with hepatic carcinoma was evaluated during the perioperative period according to the pain index. The apoptotic rate of hepatic carcinoma cells was analyzed in tumor tissues using TUNEL assay. The expression levels of apoptosis-associated proteins were detected in liver cancer cells following anesthesia in patients. Phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and nuclear factor (NF)-κB signaling pathways were also analyzed in liver cancer cells following treatment with isoflurane. The results demonstrated that isoflurane inhibited growth and decreased viability of liver cancer cells in vitro and in vivo. In addition, the apoptotic rate was increased in cells obtained from isoflurane-treated patients. The results also demonstrated that isoflurane upregulated the expression levels of proapoptotic genes and downregulated anti-apoptotic mRNA expression. In addition, a molecular mechanism analysis indicated that isoflurane inhibited PI3K and AKT expression in liver cancer cells. Isoflurane also induced caspase-3 activation in liver cancer cells. Furthermore, isoflurane treatment attenuated NF-κB activity and inhibited migration and invasion of liver cancer cells. In conclusion, these findings indicated that isoflurane treatment efficiently attenuated surgical pain and inhibited tumor aggressiveness via regulation of NF-κB activity and the PI3K/AKT signaling pathway, thus suggesting that isoflurane is an efficient anesthetic drug that induces pain remission and promotes apoptosis of liver cancer cells.