Key words laryngeal squamous cell carcinoma; signal transducer and activator of transcription 3; tumor invasion
Signal transduction and activator of transcription 3 (signal transducer and activator of transcription 3, STAT3) is an important member of the family of signal transducer and activator of transcription sub STAT3 overactivation of a variety of tumor cells, leading to abnormal cell proliferation and excessive transformation , the experimental application of JAK2 (Janus kinase 2) kinase inhibitor AG490 treatment of laryngeal squamous cell carcinoma the Hep2 cell, observation of laryngeal squamous cell proliferative activity and invasiveness explore JAK2/STAT3 signal transduction pathways in the throat scales cancer invasion regulation.
1 Data and methods
1.1 AG490 inhibition of laryngeal squamous cell carcinoma Hep2 cells JAK2/STAT3 signal transduction pathway
The flow cytometry results showed that AG490 significantly inhibit the expression of p STAT3, p STAT3 expression fluorescence index of the AG490 group compared with the control group, for 24h control group (1.361 ± 0.022), AG490 – treated group (1.254 ± 0.037), The difference was statistically significant (P <0.05); at 48h control group fluorescence index (1.353 ± 0.023), AG490 – treated group (1.134 ± 0.034), the difference was statistically significant (P ≤ 0.01); the 72h control group Fluorescence Index (1.3451 ± 0.014), Effects of AG490 group (1.3451 ± 0.014), the difference was significant (P ≤ 0.01) (Figure omitted).
1.2 AG490 laryngeal carcinoma cell line Hep 2 cell proliferation activity inhibition
MTT assay showed that the control group did not inhibit the proliferation of tumor cells, Effects of AG490 after different time detection 12h after transfection showed some inhibitory effect 36h showed significant inhibitory effect of cell viability continued to decline (F = 5.26, P = 0.004).
1.3 AG490 inhibits the Hep2 cell laryngeal carcinoma cell invasion force quantitative Matrigel invasion assay the Hep2 cell invasion force of change, the results display AG490 treatment 24 h the number of invasive cells (26.923 ± 1.556) and control group (31.517 ± 2.038) difference compared statistics significance (t = 3.102, P <0.05); AG490 treatment compared to the 48h and 72h, the number of invasive cells with the control group (56.370 ± 2.552,66.813 ± 20.056) (78.070 ± 2.575,106.443 ± 2.796) difference was statistically significant (t = 10.367,19.775, P <0.01).
STAT3 in normal tissue cell signal transduction activate rapid and transient, while in many human malignancies STAT3 overactivation of expression. JAK2 STAT3 in the cytoplasm monomer, raised as the upstream kinase activation after tyrosine phosphorylation of STAT3 molecules. Our previous immunohistochemical techniques to detect the expression of STAT3 phosphorylation of STAT3 in laryngeal squamous cell carcinoma, and found that overexpression of STAT3 phosphorylation of STAT3 in laryngeal squamous cell carcinoma lymph node metastasis . In this study, AG490 blocked JAK2/STAT3 signal transduction pathway to further confirm the relationship of this pathway and tumor invasion and metastasis. In this paper, AG490 treatment laryngeal squamous cell carcinoma cell lines Hep2, demonstrated inhibition of phosphorylation of STAT3 content, while the Matrigel invasion assay AG490 can inhibit laryngeal squamous cell carcinoma Hep2 cell invasion, suggesting JAK2/STAT3 signal transduction pathway involved in laryngeal squamous cell regulation of cancer invasion. Blocking the JAK2/STAT3 signal transduction pathway can inhibit invasion of squamous cell carcinoma of the larynx, this article provides new ideas and targets for the treatment of the invasion and metastasis of laryngeal squamous cell carcinoma.