Abstract
Several studies have shown that nemo-like kinase (NLK) plays a vital role in apoptosis of cancer cells. The present research concerned effects and mechanisms of Taxol on NLK knockdown human laryngeal cancerHep-2 cell lines in vitro. Using RNAi, methyl-thiazoltetrazolium (MTT) assays, real-time RT-PCR, Western blotting and flow cytometry analysis, growth and the cell cycle progression of NLK knockdown Hep-2 cells and expression of downstream molecules were observed. Cell growth was obviously suppressed in the Taxol treated group (P<0.001, 48 hours). Cell numbers of combined Taxol-based chemotherapy with lentivirus mediated RNAi treatment group (Lv-shNLK+Taxol goup) were significantly different from NLK-specific siRNA lentivirus infected group (Lv-shNLK group) (p<0.001). Flow cytometry analysis revealed that Lv-shNLK+Taxol caused the G0/G1-phase DNA content to decrease from 44.1 to 3.33% (p<0.001) and the S-phase DNA content to increase from 38.4 to 82.0% (p<0.001), in comparison with the Lv-shNLK+Taxol group. Immunoblot analysis showed that knockdown of NLK led to significant reduction in the levels of cyclin D1, PCNA and PARP, whereas cyclin B1 was elevated in. Cell growth was also obviously suppressed in the Hep-2 cell line, knockdown of NLK making them more sensitive to Taxol treatment. NLK is expected to become a target of new laryngeal cancer gene therapies.
Highlights
Over 500 000 patients worldwide are diagnosed as squamous cell carcinoma of head and neck each year (Nestle et al, 1998). 95% of that is laryngeal squamous cell carcinoma which accounts for 5% of malignant tumors in developed countries and represents a serious threat to human health (Sanderson and Ironside, 2002).Taxol is one of the most effective antitumor agents developed in the past three decades
Taxol inhibits the expression of nemo-like kinase (NLK) in Hep-2 cells Expression of NLK was examined by Real-time PCR
We tested the expression of NLK at 0, 24, 48 hours treated with Taxol
Summary
Taxol is one of the most effective antitumor agents developed in the past three decades. A major obstacle to achieving successful treatment is the development of cellular taxol drug resistance (Zhang et al, 2012). The Wnt/betacatenin signaling pathway regulates various aspects of development and plays important role in tumor formation in multiple tissues and organs (such as the colon, breast, ovarian, liver, etc.) (Lee et al, 2006; Kim et al, 2008; Yuzugullu et al, 2009). In the classic Wnt/beta-catenin signaling pathway, NLK is downstream gene of transforming growth factor beta kinase (TAK1). In the Wnt signaling pathway of mammalian cells, NLK is considered as inhibitory factor of β-catenin/TCF/LEF, playing as negative regulator of Wnt/beta-catenin signaling pathway (Ishitani et al, 1999)
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