Molecular mechanisms involved in regulation of proliferation and apoptosis by STAT3 antisense oligonucleotide and chemotherapy in laryngeal cancer cells / 中华耳鼻咽喉头颈外科杂志

ABSTRACT

<p><b>OBJECTIVE</b>To study the mechanism of STAT3 antisense oligonucleotide (STAT3 AS-ON) in combination with DDP in the treatment of laryngeal cancer.</p><p><b>METHODS</b>STAT3 AS-ON, DDP, or STAT3 AS-ON + DDP was added into culture media. The expression and phosphorylation levels of STAT3 protein in Hep-2 cells were measured by Western Blot. The expression of Cyclin D1 and Bcl-xL was also detected by Western Blot. The cell proliferation was assayed by methyl thiazolyl tetrazolium (MTT). Flow cytometry was performed to analyze the cell cycle and apoptosis.</p><p><b>RESULTS</b>STAT3 was highly expressed and phosphorylated in Hep-2 cells. Transfection of STAT3 AS-ON suppressed the expression and phosphorylation levels of STAT3 protein. Forty-eight hours after transfection, the proliferation of Hep-2 cells was inhibited in a dose-dependent manner. Inhibitory effects appeared at 24 h after transfection of STAT3 AS-ON, and became more obvious after 36 h. Seventy-two hours after transfection, the rate of apoptosis in STAT3 AS-ON + DDP group, DDP group, STAT3 AS-ON group, STAT3 S-ON group, lipidosome group and control group was 32.9%, 13.5%, 28.1%, 3.2%, 2.4%, 1.8% respectively. After the treatment of Hep-2 cells with STAT3 AS-ON and DDP for 72 h, the ratio of G1 phase was up-regulated from 55.7% to 74.9%, while that of S phase was own-regulate from 33.6% to 6.9%.</p><p><b>CONCLUSIONS</b>STAT3 AS-ON and DDP could suppress the growth of laryngeal cancer cells and induce significant apoptosis of laryngeal cancer cells. Combined use of them had a synergic effect, obviously inhibiting the activation of STAT3 signaling transduction pathway of laryngeal cancer cells. Selective inhibition of specific signaling pathway may provide a new therapeutic approach for treating laryngeal cancers.</p>