ag-490 and Nasopharyngeal-Neoplasms

To determine the effect of JAK kinase inhibitor AG490 on proliferation and apoptosis of nasopharyngeal carcinoma cell line C666-1 and explore the inhibitory effect of AG490 on STAT3 signal transduction pathway.. An experimental study.. Xi'an Ninth Hospital, Xi'an, China, from May 2015 to December 2016.. AG490 was applied to C666-1 cells. Cell proliferation was detected by MTTassay. Cell cycle and apoptosis were detected by flow cytometry. The expression of STAT3 and p-STAT3 protein was detected by immobilized Western blot.. AG490 could effectively inhibit proliferation of C666-1 cellsin vitro, and the inhibitory effect was characterized by time and concentration dependence. AG490 induced apoptosis of nasopharyngeal carcinoma cells, and apoptosis rate increased with prolongation of the time. AG490 could inhibit expression of STAT3 and p-STAT3 protein in C666-1 cells.. AG490 can down-regulate expression of STAT3 and p-STAT3 protein in C666-1 cells, inhibit proliferation of nasopharyngeal carcinoma cells and promote apoptosis of nasopharyngeal carcinoma cells.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma; Cell Cycle; Cell Proliferation; Flow Cytometry; Gene Expression Regulation, Neoplastic; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Signal Transduction; STAT3 Transcription Factor; Tyrphostins

Abnormal activation of Janus kinas/signal transducer and activator of transcription 3 (JAK-STAT3) signaling pathway is closely related to malignant transformation of cells. This study was to investigate the effects of a JAK inhibitor, AG490, on the proliferation, apoptosis, and expressions of apoptosis-related survivin and Mcl-1 genes, thus to explore the role of JAK-STAT3 signaling pathway in the regulation of cell apoptosis in nasopharyngeal carcinoma (NPC) cell line CNE-2Z.. CNE-2Z cells were treated with different doses of AG490. The cell proliferation was measured using MTT array. Cell apoptosis was assessed by flow cytometry (FCM) and Hoechst33342 fluorescence staining. The mRNA levels of STAT3, survivin and Mcl-1 were detected by reverse transcription-polymerase chain reaction (RT-PCR). The protein contents of STAT3, phosphoralated STAT3 (p-STAT3), survivin and Mcl-1 were measured by western blot.. The inhibition rates of CNE-2Z cell proliferation by 100 micromol/L AG490 were 37.95% and 52.99% at 24 and 48 h after treatment. After incubation with 50 micromol/L and 100 micromol/L AG490 for 24 h, the apoptotic rates of CNE-2Z cells were increased from 1.37% to 9.30% and 9.00%, respectively (p < 0.01); typical changes in apoptotic morphology were observed under fluorescence microscopy; moreover, activation of STAT3 was inhibited, mRNA and protein levels of Mcl-1 and survivin were down-regulated.. Blocking of JAK-STAT3 signaling pathway in CNE-2Z cells could remarkably inhibit cell proliferation and inactivate STAT3, as well as promote cell apoptosis by down-regulating Mcl-1 and survivin.

Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Humans; Inhibitor of Apoptosis Proteins; Janus Kinases; Microtubule-Associated Proteins; Myeloid Cell Leukemia Sequence 1 Protein; Nasopharyngeal Neoplasms; Proto-Oncogene Proteins c-bcl-2; RNA, Messenger; STAT3 Transcription Factor; Survivin; Tyrphostins