Abstract:

Objective To investigate whether Ixazomib induces apoptosis of esophageal squamous carcino⁃ma cells through mTOR/p70S6K signaling pathway. Methods Esophageal squamous cell carcinoma cells KYSE⁃140 and KYSE⁃150 were treated by Ixazomib，followed by CCK⁃8 and Edu assays to examine the cell proliferation.Flow cytometry was used to detect apoptosis of KYSE⁃140 and KYSE⁃150 cells，and expressions of caspase⁃3 andother apoptotic factors. The mRNA and protein expression levels of mTOR，p70S6K and 4E⁃BP1 were examined byRT⁃qPCR and western blot. Expressions of p⁃p70S6KThr421/Ser424 and p⁃4E⁃BP1Thr36 were detected by westernblot. Results Proliferations of KYSE⁃140 and KYSE⁃150 cells were inhibited by Ixazomib treatment in a dose⁃dependent manner. After Ixazomib treatment ，apoptosis of KYSE⁃140 and KYSE⁃150 cells were significantlyinduced（P < 0.05）and the activity of caspase⁃3 was significantly increased（P < 0.05）. The PARP was cleaved inIxazomib treatment group，whereas there was no PARP cleavage in control group. Also，the expression of apoptosisactivator p⁃p38 was significantly increased in Ixazomib treatment group（P < 0.05）. Compared with the controlgroup，Ixazomib treatment caused inhibition of the mRNA and protein expression of mTOR（P < 0.05），decreasedexpression of p70S6K and 4E⁃BP1 mRNA expression（P < 0.05）. Western blot results showed that expressions ofp⁃p70S6KThr421/Ser424 and p⁃4E⁃BP1Thr36 were significantly decreased（P < 0.05）. Conclusion Ixazomibmay induce apoptosis of esophageal squamous carcinoma cells by inhibiting mTOR / p70S6K signaling pathway.

Key words: Ixazomib, esophageal squamous cell carcinoma, mTOR/p70S6K signaling pathway,
apoptosis